rs114149451

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004260.4(RECQL4):c.3058G>A(p.Val1020Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,612,228 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1020L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0028 ( 4 hom., cov: 35)

Exomes 𝑓: 0.0011 ( 20 hom. )

Consequence

RECQL4
NM_004260.4 missense, splice_region

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

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 -16 ACMG points.

BP6

Variant 8-144512322-C-T is Benign according to our data. Variant chr8-144512322-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 135146.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144512322-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00284 (432/152380) while in subpopulation AFR AF= 0.00621 (258/41576). AF 95% confidence interval is 0.00558. There are 4 homozygotes in gnomad4. There are 200 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RECQL4	NM_004260.4 linkuse as main transcript	c.3058G>A	p.Val1020Met	missense_variant, splice_region_variant	18/21	ENST00000617875.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RECQL4	ENST00000617875.6 linkuse as main transcript	c.3058G>A	p.Val1020Met	missense_variant, splice_region_variant	18/21	1	NM_004260.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00282

AC:

429

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00615

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.0377

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00229

AC:

564

AN:

246716

Hom.:

AF XY:

0.00206

AC XY:

277

AN XY:

134656

show subpopulations

Gnomad AFR exome

AF:

0.00643

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.0354

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000495

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.00110

AC:

1606

AN:

1459848

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

799

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.00672

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000385

Gnomad4 NFE exome

AF:

0.000197

Gnomad4 OTH exome

AF:

0.00270

GnomAD4 genome

AF:

0.00284

AC:

432

AN:

152380

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

200

AN XY:

74522

show subpopulations

Gnomad4 AFR

AF:

0.00621

Gnomad4 AMR

AF:

0.000979

Gnomad4 ASJ

AF:

0.0377

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00245

Hom.:

Bravo

AF:

0.00338

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00569

AC:

ESP6500EA

AF:

0.00225

AC:

ExAC

AF:

0.00187

AC:

225

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 18, 2016	- -
not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 03, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	RECQL4: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 13, 2020	- -

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

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

Cadd

Benign

2.1

Dann

Benign

0.82

DEOGEN2

Benign

0.014

T;T;T

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.63

T;T;T

MetaRNN

Benign

0.0026

T;T;T

PrimateAI

Benign

0.37

Sift4G

Benign

0.22

T;T;T

Polyphen

0.0040

.;B;.

Vest4

0.082

MVP

0.35

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.059

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.36

Position offset: 3

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