rs1026024

Positions:

• chr12-65055206-G-A
• chr12-65055206-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_007191.5(WIF1):​c.930C>T​(p.Cys310=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,613,390 control chromosomes in the GnomAD database, including 990 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (115 hom., cov: 33)
  • Exomes 𝑓: 0.011 (875 hom.)
• Consequence: WIF1 NM_007191.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.432

Genes affected

WIF1 (HGNC:18081): (WNT inhibitory factor 1) The protein encoded by this gene functions to inhibit WNT proteins, which are extracellular signaling molecules that play a role in embryonic development. This protein contains a WNT inhibitory factor (WIF) domain and five epidermal growth factor (EGF)-like domains, and is thought to be involved in mesoderm segmentation. This gene functions as a tumor suppressor gene, and has been found to be epigenetically silenced in various cancers. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 12-65055206-G-A is Benign according to our data. Variant chr12-65055206-G-A is described in ClinVar as [Benign]. Clinvar id is 1236341.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.432 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIF1	NM_007191.5	c.930C>T	p.Cys310=	synonymous_variant	9/10	ENST00000286574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIF1	ENST00000286574.9	c.930C>T	p.Cys310=	synonymous_variant	9/10	1	NM_007191.5	P1
WIF1	ENST00000543094.1	c.177C>T	p.Cys59=	synonymous_variant	4/5	5

Frequencies

GnomAD3 genomes AF: 0.0123 AC: 1876 AN: 152138 Hom.: 116 Cov.: 33

Gnomad AFR AF: 0.00285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0274

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.0303 AC: 7592 AN: 250564 Hom.: 477 AF XY: 0.0289 AC XY: 3917 AN XY: 135382

Gnomad AFR exome AF: 0.00246

Gnomad AMR exome AF: 0.0627

Gnomad ASJ exome AF: 0.00219

Gnomad EAS exome AF: 0.183

Gnomad SAS exome AF: 0.0601

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.000538

Gnomad OTH exome AF: 0.0199

GnomAD4 exome AF: 0.0105 AC: 15357 AN: 1461134 Hom.: 875 Cov.: 30 AF XY: 0.0116 AC XY: 8429 AN XY: 726818

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.0578

Gnomad4 ASJ exome AF: 0.00168

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.0602

Gnomad4 FIN exome AF: 0.000225

Gnomad4 NFE exome AF: 0.000316

Gnomad4 OTH exome AF: 0.0209

GnomAD4 genome AF: 0.0123 AC: 1869 AN: 152256 Hom.: 115 Cov.: 33 AF XY: 0.0146 AC XY: 1086 AN XY: 74436

Gnomad4 AFR AF: 0.00284

Gnomad4 AMR AF: 0.0272

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00556 Hom.: 26

Bravo AF: 0.0148

Asia WGS AF: 0.125 AC: 434 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.8
DANN	Benign	0.56

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: rs1026024; hg19: chr12-65448986; COSMIC: COSV54132153; COSMIC: COSV54132153;