8-144516318-C-G

Position:

chr8-144516318-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004260.4(RECQL4):c.801G>C(p.Glu267Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,608,224 control chromosomes in the GnomAD database, including 137,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

Frequency

Genomes: 𝑓 0.42 ( 13793 hom., cov: 34)

Exomes 𝑓: 0.41 ( 123432 hom. )

Consequence

RECQL4
NM_004260.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10O:1

Conservation

PhyloP100: -1.07

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.5492116E-5).

BP6

Variant 8-144516318-C-G is Benign according to our data. Variant chr8-144516318-C-G is described in ClinVar as [Benign]. Clinvar id is 94898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144516318-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.801G>C	p.Glu267Asp	missense_variant	5/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RECQL4	ENST00000617875.6 linkuse as main transcript	c.801G>C	p.Glu267Asp	missense_variant	5/21	1	NM_004260.4	P1
RECQL4	ENST00000621189.4 linkuse as main transcript	c.-271G>C		5_prime_UTR_variant	4/20	1
RECQL4	ENST00000524998.1 linkuse as main transcript	c.324G>C	p.Glu108Asp	missense_variant	3/4	3
RECQL4	ENST00000534538.1 linkuse as main transcript	c.*605G>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.422

AC:

64160

AN:

151954

Hom.:

13773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.454

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.403

Gnomad OTH

AF:

0.435

GnomAD3 exomes

AF:

0.437

AC:

105355

AN:

240852

Hom.:

23175

AF XY:

0.435

AC XY:

57211

AN XY:

131396

show subpopulations

Gnomad AFR exome

AF:

0.426

Gnomad AMR exome

AF:

0.534

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.450

Gnomad SAS exome

AF:

0.498

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.413

GnomAD4 exome

AF:

0.409

AC:

596009

AN:

1456152

Hom.:

123432

Cov.:

AF XY:

0.412

AC XY:

298362

AN XY:

724102

show subpopulations

Gnomad4 AFR exome

AF:

0.428

Gnomad4 AMR exome

AF:

0.524

Gnomad4 ASJ exome

AF:

0.377

Gnomad4 EAS exome

AF:

0.395

Gnomad4 SAS exome

AF:

0.497

Gnomad4 FIN exome

AF:

0.417

Gnomad4 NFE exome

AF:

0.399

Gnomad4 OTH exome

AF:

0.409

GnomAD4 genome

AF:

0.422

AC:

64221

AN:

152072

Hom.:

13793

Cov.:

AF XY:

0.427

AC XY:

31713

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.426

Gnomad4 AMR

AF:

0.483

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.453

Gnomad4 SAS

AF:

0.512

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.403

Gnomad4 OTH

AF:

0.434

Alfa

AF:

0.406

Hom.:

2917

Bravo

AF:

0.427

TwinsUK

AF:

0.395

AC:

1466

ALSPAC

AF:

0.398

AC:

1534

ESP6500AA

AF:

0.410

AC:

1614

ESP6500EA

AF:

0.383

AC:

3184

ExAC

AF:

0.426

AC:

51219

Asia WGS

AF:

0.515

AC:

1790

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4Other:1

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	-	- -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Rothmund-Thomson syndrome type 2

Benign:2

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

Baller-Gerold syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -

Rapadilino syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 26, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.28

DANN

Benign

0.44

DEOGEN2

Benign

0.031

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.38

MetaRNN

Benign

0.000085

PrimateAI

Benign

0.28

Sift4G

Benign

0.31

Polyphen

0.0020

Vest4

0.067

GERP RS

-3.0

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.0

Varity_R

0.034

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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