rs116757787

Variant names:

• chr2-174567080-G-A
• rs116757787
• NM_001375834.1:c.1446C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001375834.1(WIPF1):​c.1446C>T​(p.Asn482Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,614,080 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0094 (7 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (49 hom.)
• Consequence: WIPF1 NM_001375834.1 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0170
• Publications: 3 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 2-174567080-G-A is Benign according to our data. Variant chr2-174567080-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 403609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.017 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00945 (1439/152288) while in subpopulation AFR AF = 0.018 (748/41546). AF 95% confidence interval is 0.0169. There are 7 homozygotes in GnomAd4. There are 641 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	NM_001375834.1	MANE Select	c.1446C>T	p.Asn482Asn	synonymous	Exon 7 of 8	NP_001362763.1	A0A140VJZ9
	WIPF1	NM_001375835.1		c.1446C>T	p.Asn482Asn	synonymous	Exon 7 of 9	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.1446C>T	p.Asn482Asn	synonymous	Exon 7 of 8	NP_001070737.1	Q2YDC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	ENST00000679041.1	MANE Select	c.1446C>T	p.Asn482Asn	synonymous	Exon 7 of 8	ENSP00000503603.1	O43516-1
	WIPF1	ENST00000272746.9	TSL:1	c.1446C>T	p.Asn482Asn	synonymous	Exon 7 of 9	ENSP00000272746.5	O43516-3
	WIPF1	ENST00000359761.7	TSL:1	c.1446C>T	p.Asn482Asn	synonymous	Exon 7 of 8	ENSP00000352802.3	O43516-1

Frequencies

GnomAD3 genomes AF: 0.00945 AC: 1438 AN: 152170 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00655

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00544 AC: 1369 AN: 251458 AF XY: 0.00498

Gnomad AFR exome AF: 0.0187

Gnomad AMR exome AF: 0.00552

Gnomad ASJ exome AF: 0.0143

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000970

Gnomad NFE exome AF: 0.00582

Gnomad OTH exome AF: 0.00750

GnomAD4 exome AF: 0.00632 AC: 9245 AN: 1461792 Hom.: 49 Cov.: 31 AF XY: 0.00613 AC XY: 4460 AN XY: 727198

African (AFR) AF: 0.0191 AC: 639 AN: 33468

American (AMR) AF: 0.00572 AC: 256 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 325 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000464 AC: 4 AN: 86256

European-Finnish (FIN) AF: 0.00131 AC: 70 AN: 53418

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.00676 AC: 7519 AN: 1111934

Other (OTH) AF: 0.00705 AC: 426 AN: 60390

GnomAD4 genome AF: 0.00945 AC: 1439 AN: 152288 Hom.: 7 Cov.: 33 AF XY: 0.00861 AC XY: 641 AN XY: 74472

African (AFR) AF: 0.0180 AC: 748 AN: 41546

American (AMR) AF: 0.0105 AC: 161 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 46 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00656 AC: 446 AN: 68034

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00820 Hom.: 4

Bravo AF: 0.0106

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00627

EpiControl AF: 0.00688

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Wiskott-Aldrich syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.5
DANN	Benign	0.91
PhyloP100		0.017
Mutation Taster		=100/0	polymorphism

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: rs116757787; hg19: chr2-175431808;