Genetic Variant WIPF1:c.-38-44972G>A (chr2-174630583-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001375835.1(WIPF1):c.-38-44972G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,994 control chromosomes in the GnomAD database, including 8,008 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 8008 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

WIPF1
NM_001375835.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.20

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

WIPF1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375835.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
WIPF1	NM_001375835.1	c.-38-44972G>A	intron	N/A	NP_001362764.1	O43516-3
WIPF1	NM_001077269.1	c.-38-44972G>A	intron	N/A	NP_001070737.1	Q2YDC4
WIPF1	NM_001375832.1	c.-241-715G>A	intron	N/A	NP_001362761.1	O43516-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WIPF1	ENST00000272746.9	TSL:1	c.-38-44972G>A	intron	N/A	ENSP00000272746.5	O43516-3
WIPF1	ENST00000359761.7	TSL:1	c.-38-44972G>A	intron	N/A	ENSP00000352802.3	O43516-1
WIPF1	ENST00000392547.6	TSL:1	c.-39+3935G>A	intron	N/A	ENSP00000376330.2	O43516-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

45000

AN:

151876

Hom.:

8000

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.291

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.294

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.296

AC:

45034

AN:

151994

Hom.:

8008

Cov.:

AF XY:

0.305

AC XY:

22666

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.140

AC:

5801

AN:

41462

American (AMR)

AF:

0.449

AC:

6849

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1009

AN:

3472

East Asian (EAS)

AF:

0.669

AC:

3450

AN:

5160

South Asian (SAS)

AF:

0.376

AC:

1815

AN:

4826

European-Finnish (FIN)

AF:

0.367

AC:

3872

AN:

10548

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21161

AN:

67958

Other (OTH)

AF:

0.293

AC:

615

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1480

2960

4439

5919

7399

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.297

Hom.:

12163

Bravo

AF:

0.297

Asia WGS

AF:

0.478

AC:

1663

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.50

(source)

DANN

Benign

0.80

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over