chr12-65056267-C-CT

Position:

• chr12-65056267-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_007191.5(WIF1):​c.827-142_827-141insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0549 in 475,434 control chromosomes in the GnomAD database, including 750 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (728 hom., cov: 31)
  • Exomes 𝑓: 0.047 (22 hom.)
• Consequence: WIF1 NM_007191.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.28

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 -10 ACMG points.

• BP6: Variant 12-65056267-C-CT is Benign according to our data. Variant chr12-65056267-C-CT is described in ClinVar as [Benign]. Clinvar id is 1181766.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIF1	NM_007191.5	c.827-142_827-141insA		intron_variant		ENST00000286574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIF1	ENST00000286574.9	c.827-142_827-141insA		intron_variant		1	NM_007191.5	P1
WIF1	ENST00000543094.1	c.116-142_116-141insA		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 9148 AN: 117960 Hom.: 725 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0278

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00646

Gnomad SAS AF: 0.0617

Gnomad FIN AF: 0.00190

Gnomad MID AF: 0.0658

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0748

GnomAD4 exome AF: 0.0474 AC: 16953 AN: 357464 Hom.: 22 AF XY: 0.0483 AC XY: 8939 AN XY: 185130

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.0579

Gnomad4 ASJ exome AF: 0.0532

Gnomad4 EAS exome AF: 0.0410

Gnomad4 SAS exome AF: 0.0723

Gnomad4 FIN exome AF: 0.0330

Gnomad4 NFE exome AF: 0.0388

Gnomad4 OTH exome AF: 0.0604

GnomAD4 genome AF: 0.0776 AC: 9151 AN: 117970 Hom.: 728 Cov.: 31 AF XY: 0.0780 AC XY: 4378 AN XY: 56154

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.0378

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00621

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.00190

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0746

Bravo AF: 0.0683

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 19, 2021

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Computational scores

Source: dbNSFP v4.3

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: rs370267621; hg19: chr12-65450047;