Variant 6-110101728-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_003931.3(WASF1):c.1382C>T(p.Thr461Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,614,180 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 7 hom. )

Consequence

WASF1
NM_003931.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

WASF1 (HGNC:12732): (WASP family member 1) The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

WASF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 6-110101728-G-A is Benign according to our data. Variant chr6-110101728-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2656838.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 160 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASF1	NM_003931.3 linkuse as main transcript	c.1382C>T	p.Thr461Ile	missense_variant	10/11	ENST00000392589.6	NP_003922.1	Q92558
WASF1	NM_001024934.2 linkuse as main transcript	c.1382C>T	p.Thr461Ile	missense_variant	9/10		NP_001020105.1	Q92558
WASF1	NM_001024935.2 linkuse as main transcript	c.1382C>T	p.Thr461Ile	missense_variant	9/10		NP_001020106.1	Q92558
WASF1	NM_001024936.2 linkuse as main transcript	c.1382C>T	p.Thr461Ile	missense_variant	8/9		NP_001020107.1	Q92558

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASF1	ENST00000392589.6 linkuse as main transcript	c.1382C>T	p.Thr461Ile	missense_variant	10/11	5	NM_003931.3	ENSP00000376368.1		Q92558

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00111

AC:

278

AN:

251368

Hom.:

AF XY:

0.00124

AC XY:

169

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00145

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00143

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00138

AC:

2016

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00139

AC XY:

1008

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00204

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00147

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.00105

AC:

160

AN:

152306

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00141

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.000869

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00107

AC:

130

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00180

EpiControl

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

WASF1: BS1 -

WASF1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.055

T;T;T;T;T

Eigen

Benign

-0.10

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.66

.;.;.;.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0054

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;N;N;N;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.24

N;N;N;N;N

REVEL

Benign

0.067

Sift

Benign

0.35

T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.088

MVP

0.082

MPC

0.60

ClinPred

0.017

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: -9

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