dbSNP rs559167672: RECQL4:p.Val148Val (chr8-144516675-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_004260.4(RECQL4):c.444C>T(p.Val148Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000119 in 1,591,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

RECQL4
NM_004260.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.93

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 8-144516675-G-A is Benign according to our data. Variant chr8-144516675-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 459500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.93 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RECQL4	NM_004260.4 link	c.444C>T	p.Val148Val	synonymous_variant	Exon 5 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.444C>T	p.Val148Val	synonymous_variant	Exon 5 of 21	1	NM_004260.4	ENSP00000482313.2		O94761

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000171

AC:

AN:

228374

Hom.:

AF XY:

0.000194

AC XY:

AN XY:

123962

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000124

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000769

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000122

AC:

175

AN:

1438792

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

110

AN XY:

713786

show subpopulations

Gnomad4 AFR exome

AF:

0.000184

Gnomad4 AMR exome

AF:

0.0000472

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000989

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000681

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000120

Hom.:

Bravo

AF:

0.0000907

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Rapadilino syndrome

Benign:1

Feb 01, 2025

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

RECQL4: BP4, BP7 -

Rothmund-Thomson syndrome type 2

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:1

Nov 03, 2021

Sema4, Sema4

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: curation

- -

Baller-Gerold syndrome

Benign:1

Jan 23, 2025

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

-0.90

CADD

Benign

0.43

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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