8-144515238-C-T

Position:

chr8-144515238-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004260.4(RECQL4):c.1395G>A(p.Thr465Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00692 in 1,591,106 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 7 hom., cov: 34)

Exomes 𝑓: 0.0071 ( 56 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.61

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 links:

RECQL4 (HGNC:):

RECQL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-144515238-C-T is Benign according to our data. Variant chr8-144515238-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 198789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144515238-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.61 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0053 (808/152336) while in subpopulation NFE AF= 0.0092 (626/68014). AF 95% confidence interval is 0.00861. There are 7 homozygotes in gnomad4. There are 322 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.1395G>A	p.Thr465Thr	synonymous_variant	8/21	ENST00000617875.6	NP_004251.4	O94761

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RECQL4	ENST00000617875.6 linkuse as main transcript	c.1395G>A	p.Thr465Thr	synonymous_variant	8/21	1	NM_004260.4	ENSP00000482313.2	O94761
RECQL4	ENST00000621189.4 linkuse as main transcript	c.324G>A	p.Thr108Thr	synonymous_variant	7/20	1		ENSP00000483145.1	A0A087X072
RECQL4	ENST00000532846.2 linkuse as main transcript	c.279G>A	p.Thr93Thr	synonymous_variant	4/9	5		ENSP00000476551.1	V9GYA3
RECQL4	ENST00000688394.1 linkuse as main transcript	n.418G>A		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes

AF:

0.00531

AC:

808

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00920

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00542

AC:

1156

AN:

213264

Hom.:

AF XY:

0.00539

AC XY:

624

AN XY:

115820

show subpopulations

Gnomad AFR exome

AF:

0.000734

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00825

Gnomad EAS exome

AF:

0.0000659

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.00367

Gnomad NFE exome

AF:

0.00919

Gnomad OTH exome

AF:

0.00814

GnomAD4 exome

AF:

0.00709

AC:

10203

AN:

1438770

Hom.:

Cov.:

AF XY:

0.00703

AC XY:

5018

AN XY:

713812

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00151

Gnomad4 ASJ exome

AF:

0.0101

Gnomad4 EAS exome

AF:

0.0000522

Gnomad4 SAS exome

AF:

0.00117

Gnomad4 FIN exome

AF:

0.00373

Gnomad4 NFE exome

AF:

0.00834

Gnomad4 OTH exome

AF:

0.00606

GnomAD4 genome

AF:

0.00530

AC:

808

AN:

152336

Hom.:

Cov.:

AF XY:

0.00432

AC XY:

322

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00920

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00817

Hom.:

Bravo

AF:

0.00477

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	RECQL4: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 10, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 18, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Apr 08, 2015	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2024

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. -

Rothmund-Thomson syndrome type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Baller-Gerold syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hereditary cancer-predisposing syndrome

Benign:1

Likely benign, criteria provided, single submitter

curation

Sema4, Sema4

May 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.030

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over