12-65055206-G-A

Variant names:

• chr12-65055206-G-A
• rs1026024
• NM_007191.5:c.930C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007191.5(WIF1):​c.930C>T​(p.Cys310Cys) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.432
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -21 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 VariationId is 1236341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007191.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIF1	NM_007191.5	MANE Select	c.930C>T	p.Cys310Cys	synonymous	Exon 9 of 10	NP_009122.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIF1	ENST00000286574.9	TSL:1 MANE Select	c.930C>T	p.Cys310Cys	synonymous	Exon 9 of 10	ENSP00000286574.4
	WIF1	ENST00000543094.1	TSL:5	c.177C>T	p.Cys59Cys	synonymous	Exon 4 of 5	ENSP00000439024.1

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

GnomAD2 exomes AF: 0.0303 AC: 7592 AN: 250564 AF XY: 0.0289

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 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

African (AFR) AF: 0.00152 AC: 51 AN: 33448

American (AMR) AF: 0.0578 AC: 2576 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.00168 AC: 44 AN: 26114

East Asian (EAS) AF: 0.148 AC: 5870 AN: 39678

South Asian (SAS) AF: 0.0602 AC: 5178 AN: 86010

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53408

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5764

European-Non Finnish (NFE) AF: 0.000316 AC: 351 AN: 1111766

Other (OTH) AF: 0.0209 AC: 1260 AN: 60364

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

African (AFR) AF: 0.00284 AC: 118 AN: 41542

American (AMR) AF: 0.0272 AC: 416 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.175 AC: 910 AN: 5186

South Asian (SAS) AF: 0.0742 AC: 358 AN: 4826

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

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

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68022

Other (OTH) AF: 0.0156 AC: 33 AN: 2114

Alfa AF: 0.00620 Hom.: 41

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	5.8
DANN	Benign	0.56
PhyloP100		-0.43
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: rs1026024; hg19: chr12-65448986; COSMIC: COSV54132153; COSMIC: COSV54132153;