dbSNP rs35923393: WIPF1:p.Asn26Asn (chr2-174581413-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001375834.1(WIPF1):c.78T>C(p.Asn26Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00216 in 1,613,924 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 Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

WIPF1
NM_001375834.1 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.84

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Wiskott-Aldrich syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
Wiskott-Aldrich syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WIPF1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

ENSG00000237798 (HGNC:40613):

ENSG00000237798 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 2-174581413-A-G is Benign according to our data. Variant chr2-174581413-A-G is described in ClinVar as Benign. ClinVar VariationId is 472923.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.85 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375834.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
WIPF1	NM_001375834.1	MANE Select	c.78T>C	p.Asn26Asn	synonymous	Exon 3 of 8	NP_001362763.1
WIPF1	NM_001375835.1		c.78T>C	p.Asn26Asn	synonymous	Exon 3 of 9	NP_001362764.1
WIPF1	NM_001077269.1		c.78T>C	p.Asn26Asn	synonymous	Exon 3 of 8	NP_001070737.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
WIPF1	ENST00000679041.1	MANE Select	c.78T>C	p.Asn26Asn	synonymous	Exon 3 of 8	ENSP00000503603.1
WIPF1	ENST00000272746.9	TSL:1	c.78T>C	p.Asn26Asn	synonymous	Exon 3 of 9	ENSP00000272746.5
WIPF1	ENST00000359761.7	TSL:1	c.78T>C	p.Asn26Asn	synonymous	Exon 3 of 8	ENSP00000352802.3

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

265

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00953

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00212

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.00185

AC:

466

AN:

251400

AF XY:

0.00199

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00832

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00221

AC:

3226

AN:

1461708

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

1595

AN XY:

727152

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33472

American (AMR)

AF:

0.0000447

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00916

AC:

489

AN:

53370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00239

AC:

2662

AN:

1111922

Other (OTH)

AF:

0.00104

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

178

356

534

712

890

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00174

AC:

265

AN:

152216

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000385

AC:

AN:

41520

American (AMR)

AF:

0.000196

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00953

AC:

101

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00212

AC:

144

AN:

68022

Other (OTH)

AF:

0.000476

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00109

EpiCase

AF:

0.00125

EpiControl

AF:

0.00166

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wiskott-Aldrich syndrome 2

Benign:1

Jan 18, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

WIPF1-related disorder

Benign:1

Feb 14, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

6.5

(source)

DANN

Benign

0.78

PhyloP100

1.8

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over