chr12-65055962-T-C

Position:

• chr12-65055962-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007191.5(WIF1):​c.922+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,393,370 control chromosomes in the GnomAD database, including 1,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.062 (786 hom., cov: 32)
  • Exomes 𝑓: 0.017 (877 hom.)
• Consequence: WIF1 NM_007191.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.88

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-65055962-T-C is Benign according to our data. Variant chr12-65055962-T-C is described in ClinVar as [Benign]. Clinvar id is 1222654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIF1	NM_007191.5	c.922+69A>G		intron_variant		ENST00000286574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIF1	ENST00000286574.9	c.922+69A>G		intron_variant		1	NM_007191.5	P1
WIF1	ENST00000543094.1	c.169+111A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9477 AN: 152154 Hom.: 780 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00967

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0169 AC: 21025 AN: 1241098 Hom.: 877 AF XY: 0.0176 AC XY: 11000 AN XY: 625174

Gnomad4 AFR exome AF: 0.201

Gnomad4 AMR exome AF: 0.0154

Gnomad4 ASJ exome AF: 0.0145

Gnomad4 EAS exome AF: 0.000546

Gnomad4 SAS exome AF: 0.0514

Gnomad4 FIN exome AF: 0.00134

Gnomad4 NFE exome AF: 0.00956

Gnomad4 OTH exome AF: 0.0246

GnomAD4 genome AF: 0.0624 AC: 9496 AN: 152272 Hom.: 786 Cov.: 32 AF XY: 0.0612 AC XY: 4557 AN XY: 74462

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0489

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00967

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0310 Hom.: 164

Bravo AF: 0.0683

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.043
DANN	Benign	0.34

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: rs12317641; hg19: chr12-65449742;