rs4244613

Positions:

chr8-144516381-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000617875.6(RECQL4):c.738C>T(p.Ser246=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,609,020 control chromosomes in the GnomAD database, including 154,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 11816 hom., cov: 34)

Exomes 𝑓: 0.44 ( 142394 hom. )

Consequence

RECQL4
ENST00000617875.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.05

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 8-144516381-G-A is Benign according to our data. Variant chr8-144516381-G-A is described in ClinVar as [Benign]. Clinvar id is 94897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144516381-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.738C>T	p.Ser246=	synonymous_variant	5/21	ENST00000617875.6	NP_004251.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
RECQL4	ENST00000617875.6 linkuse as main transcript	c.738C>T	p.Ser246=	synonymous_variant	5/21	1	NM_004260.4	ENSP00000482313	P1
RECQL4	ENST00000621189.4 linkuse as main transcript	c.-334C>T		5_prime_UTR_variant	4/20	1		ENSP00000483145
RECQL4	ENST00000524998.1 linkuse as main transcript	c.261C>T	p.Ser87=	synonymous_variant	3/4	3		ENSP00000476579
RECQL4	ENST00000534538.1 linkuse as main transcript	c.*542C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	3		ENSP00000476318

Frequencies

GnomAD3 genomes

AF:

0.369

AC:

56126

AN:

152024

Hom.:

11812

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.491

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.384

GnomAD3 exomes

AF:

0.444

AC:

107810

AN:

242800

Hom.:

24935

AF XY:

0.447

AC XY:

59336

AN XY:

132650

show subpopulations

Gnomad AFR exome

AF:

0.145

Gnomad AMR exome

AF:

0.532

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.452

Gnomad SAS exome

AF:

0.507

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.439

Gnomad OTH exome

AF:

0.429

GnomAD4 exome

AF:

0.438

AC:

637528

AN:

1456878

Hom.:

142394

Cov.:

AF XY:

0.440

AC XY:

319175

AN XY:

724690

show subpopulations

Gnomad4 AFR exome

AF:

0.143

Gnomad4 AMR exome

AF:

0.519

Gnomad4 ASJ exome

AF:

0.359

Gnomad4 EAS exome

AF:

0.396

Gnomad4 SAS exome

AF:

0.507

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.420

GnomAD4 genome

AF:

0.369

AC:

56144

AN:

152142

Hom.:

11816

Cov.:

AF XY:

0.377

AC XY:

28017

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.159

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.522

Gnomad4 FIN

AF:

0.491

Gnomad4 NFE

AF:

0.442

Gnomad4 OTH

AF:

0.383

Alfa

AF:

0.403

Hom.:

3850

Bravo

AF:

0.357

Asia WGS

AF:

0.501

AC:

1742

AN:

3478

EpiCase

AF:

0.434

EpiControl

AF:

0.434

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Mar 16, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Rothmund-Thomson syndrome type 2

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	KCCC/NGS Laboratory, Kuwait Cancer Control Center	Jul 07, 2023	- -

Baller-Gerold syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Rapadilino syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.25

DANN

Benign

0.68

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