2-174603041-T-C

Variant names:

• chr2-174603041-T-C
• rs1991601
• ENST00000272746.9:c.-38-17430A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375835.1(WIPF1):​c.-38-17430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 152,082 control chromosomes in the GnomAD database, including 48,587 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 0.80 (48587 hom., cov: 31)
• Consequence: WIPF1 NM_001375835.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109
• Publications: 14 publications found

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

ENSG00000236449 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.967 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	NM_001375835.1		c.-38-17430A>G		intron	N/A	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.-38-17430A>G		intron	N/A	NP_001070737.1	Q2YDC4
	WIPF1	NM_001375832.1		c.-38-17430A>G		intron	N/A	NP_001362761.1	O43516-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	ENST00000272746.9	TSL:1	c.-38-17430A>G		intron	N/A	ENSP00000272746.5	O43516-3
	WIPF1	ENST00000359761.7	TSL:1	c.-38-17430A>G		intron	N/A	ENSP00000352802.3	O43516-1
	WIPF1	ENST00000392547.6	TSL:1	c.-38-17430A>G		intron	N/A	ENSP00000376330.2	O43516-1

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121093 AN: 151964 Hom.: 48527 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.758

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.797 AC: 121210 AN: 152082 Hom.: 48587 Cov.: 31 AF XY: 0.802 AC XY: 59647 AN XY: 74356

African (AFR) AF: 0.792 AC: 32856 AN: 41472

American (AMR) AF: 0.822 AC: 12552 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2393 AN: 3470

East Asian (EAS) AF: 0.990 AC: 5133 AN: 5186

South Asian (SAS) AF: 0.841 AC: 4050 AN: 4814

European-Finnish (FIN) AF: 0.825 AC: 8739 AN: 10592

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53110 AN: 67968

Other (OTH) AF: 0.754 AC: 1588 AN: 2106

Alfa AF: 0.777 Hom.: 92564

Bravo AF: 0.794

Asia WGS AF: 0.871 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.72
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1991601; hg19: chr2-175467769;