2-174603041-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ENSG00000236449 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF1	XM_047445750.1	c.-4904A>G		5_prime_UTR_variant	Exon 6 of 13		XP_047301706.1
WIPF1	XM_047445757.1	c.-5167A>G		5_prime_UTR_variant	Exon 9 of 17		XP_047301713.1
WIPF1	NM_001375835.1	c.-38-17430A>G		intron_variant	Intron 1 of 8		NP_001362764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000272746.9	c.-38-17430A>G		intron_variant	Intron 1 of 8	1		ENSP00000272746.5
WIPF1	ENST00000359761.7	c.-38-17430A>G		intron_variant	Intron 1 of 7	1		ENSP00000352802.3
WIPF1	ENST00000392547.6	c.-38-17430A>G		intron_variant	Intron 1 of 7	1		ENSP00000376330.2

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

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.990

Gnomad4 SAS AF: 0.841

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.754

Alfa AF: 0.776 Hom.: 67193

Bravo AF: 0.794

Asia WGS AF: 0.871 AC: 3027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.2
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs1991601; hg19: chr2-175467769;