chr8-144514338-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_004260.4(RECQL4):c.1729C>T(p.Leu577Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000138 in 1,454,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L577L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.36

Publications

1 publications found

Variant links:

Genes affected

RECQL4 (HGNC:9949): (RecQ like helicase 4) The protein encoded by this gene is a DNA helicase that belongs to the RecQ helicase family. DNA helicases unwind double-stranded DNA into single-stranded DNAs and may modulate chromosome segregation. This gene is predominantly expressed in thymus and testis. Mutations in this gene are associated with Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. [provided by RefSeq, Jan 2010]

RECQL4 Gene-Disease associations (from GenCC):

Baller-Gerold syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet
Rothmund-Thomson syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Rothmund-Thomson syndrome type 2
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp, G2P
osteosarcoma
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
rapadilino syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp

RECQL4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 8-144514338-G-A is Benign according to our data. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144514338-G-A is described in CliVar as Likely_benign. Clinvar id is 459340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.1729C>T	p.Leu577Leu	synonymous_variant	Exon 11 of 21	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RECQL4	ENST00000617875.6 link	c.1729C>T	p.Leu577Leu	synonymous_variant	Exon 11 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152162

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1454544

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722872

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000300

AC:

AN:

33386

American (AMR)

AF:

0.00

AC:

AN:

44456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25890

East Asian (EAS)

AF:

0.00

AC:

AN:

39576

South Asian (SAS)

AF:

0.00

AC:

AN:

86002

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108106

Other (OTH)

AF:

0.0000166

AC:

AN:

60108

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.044843), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

African (AFR)

AF:

0.00

AC:

AN:

41418

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Nov 17, 2024

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Baller-Gerold syndrome

Benign:1

Oct 26, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

3.7

(source)

DANN

Benign

0.59

PhyloP100

4.4

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over