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GeneBe

2-174567113-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001375834.1(WIPF1):c.1413G>A(p.Thr471=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,614,146 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00052 ( 7 hom. )

Consequence

WIPF1
NM_001375834.1 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.738
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-174567113-C-T is Benign according to our data. Variant chr2-174567113-C-T is described in ClinVar as [Benign]. Clinvar id is 472920.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.738 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0048 (731/152276) while in subpopulation AFR AF= 0.0169 (704/41544). AF 95% confidence interval is 0.0159. There are 3 homozygotes in gnomad4. There are 314 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WIPF1NM_001375834.1 linkuse as main transcriptc.1413G>A p.Thr471= synonymous_variant 7/8 ENST00000679041.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WIPF1ENST00000679041.1 linkuse as main transcriptc.1413G>A p.Thr471= synonymous_variant 7/8 NM_001375834.1 P3O43516-1
ENST00000442996.1 linkuse as main transcriptn.217+19636C>T intron_variant, non_coding_transcript_variant 1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00480
AC:
730
AN:
152158
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0170
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00118
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00130
AC:
327
AN:
251460
Hom.:
1
AF XY:
0.000868
AC XY:
118
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.0180
Gnomad AMR exome
AF:
0.000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000515
AC:
753
AN:
1461870
Hom.:
7
Cov.:
31
AF XY:
0.000455
AC XY:
331
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0186
Gnomad4 AMR exome
AF:
0.000917
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.00108
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00480
AC:
731
AN:
152276
Hom.:
3
Cov.:
33
AF XY:
0.00422
AC XY:
314
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0169
Gnomad4 AMR
AF:
0.00118
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00258
Hom.:
3
Bravo
AF:
0.00552
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Wiskott-Aldrich syndrome 2 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
4.0
Dann
Benign
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs149092210; hg19: chr2-175431841; API