Variant 2-174585532-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001375834.1(WIPF1):c.42G>A(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,085,630 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 20 hom., cov: 28)

Exomes 𝑓: 0.0012 ( 10 hom. )

Consequence

WIPF1
NM_001375834.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.16

Variant links:

Genes affected

WIPF1 (HGNC:12736): (WAS/WASL interacting protein family member 1) This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

WIPF1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

ENSG00000237798 (HGNC:40613):

ENSG00000237798 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-174585532-C-T is Benign according to our data. Variant chr2-174585532-C-T is described in ClinVar as [Benign]. Clinvar id is 472922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1181/130498) while in subpopulation AFR AF= 0.0321 (1131/35202). AF 95% confidence interval is 0.0306. There are 20 homozygotes in gnomad4. There are 562 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF1	NM_001375834.1 link	c.42G>A	p.Thr14Thr	synonymous_variant	2/8	ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1 link	c.42G>A	p.Thr14Thr	synonymous_variant	2/8		NM_001375834.1	ENSP00000503603.1		O43516-1

Frequencies

GnomAD3 genomes

AF:

0.00905

AC:

1181

AN:

130440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00232

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000557

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000794

Gnomad OTH

AF:

0.00837

GnomAD3 exomes

AF:

0.00215

AC:

525

AN:

244346

Hom.:

AF XY:

0.00151

AC XY:

200

AN XY:

132796

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000996

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00119

AC:

1140

AN:

955132

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

486

AN XY:

483122

show subpopulations

Gnomad4 AFR exome

AF:

0.0421

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000518

Gnomad4 OTH exome

AF:

0.00285

GnomAD4 genome

AF:

0.00905

AC:

1181

AN:

130498

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

562

AN XY:

62148

show subpopulations

Gnomad4 AFR

AF:

0.0321

Gnomad4 AMR

AF:

0.00232

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000557

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000794

Gnomad4 OTH

AF:

0.00830

Alfa

AF:

0.00333

Hom.:

Bravo

AF:

0.00950

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wiskott-Aldrich syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

WIPF1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 15, 2019

This variant is classified as 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

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.4

DANN

Benign

0.86

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