rs76308107

Variant names:

• chr2-174575223-G-C
• rs76308107
• NM_001375834.1:c.339C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001375834.1(WIPF1):​c.339C>G​(p.Ser113Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,612,036 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0056 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (5 hom.)
• Consequence: WIPF1 NM_001375834.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.56
• Publications: 2 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:):

WIPF1-AS1 (HGNC:40613):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 2-174575223-G-C is Benign according to our data. Variant chr2-174575223-G-C is described in ClinVar as Benign. ClinVar VariationId is 472921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.56 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00564 (858/152224) while in subpopulation AFR AF = 0.02 (829/41514). AF 95% confidence interval is 0.0188. There are 11 homozygotes in GnomAd4. There are 401 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 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.339C>G	p.Ser113Ser	synonymous	Exon 4 of 8	NP_001362763.1	A0A140VJZ9
	WIPF1	NM_001375835.1		c.339C>G	p.Ser113Ser	synonymous	Exon 4 of 9	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.339C>G	p.Ser113Ser	synonymous	Exon 4 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.339C>G	p.Ser113Ser	synonymous	Exon 4 of 8	ENSP00000503603.1	O43516-1
	WIPF1	ENST00000272746.9	TSL:1	c.339C>G	p.Ser113Ser	synonymous	Exon 4 of 9	ENSP00000272746.5	O43516-3
	WIPF1	ENST00000359761.7	TSL:1	c.339C>G	p.Ser113Ser	synonymous	Exon 4 of 8	ENSP00000352802.3	O43516-1

Frequencies

GnomAD3 genomes AF: 0.00562 AC: 855 AN: 152106 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

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: 0.0000294

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00145 AC: 358 AN: 247622 AF XY: 0.000970

Gnomad AFR exome AF: 0.0209

Gnomad AMR exome AF: 0.000437

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000551 AC: 805 AN: 1459812 Hom.: 5 Cov.: 32 AF XY: 0.000426 AC XY: 309 AN XY: 725972

African (AFR) AF: 0.0202 AC: 676 AN: 33430

American (AMR) AF: 0.000629 AC: 28 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26024

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.000696 AC: 4 AN: 5748

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1110700

Other (OTH) AF: 0.00136 AC: 82 AN: 60284

GnomAD4 genome AF: 0.00564 AC: 858 AN: 152224 Hom.: 11 Cov.: 32 AF XY: 0.00539 AC XY: 401 AN XY: 74422

African (AFR) AF: 0.0200 AC: 829 AN: 41514

American (AMR) AF: 0.00157 AC: 24 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68002

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.00179 Hom.: 2

Bravo AF: 0.00651

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	WIPF1-related disorder (1)
-	-	1	Wiskott-Aldrich syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		2.6
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: rs76308107; hg19: chr2-175439951;