rs10506532

chr12-65111882-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007191.5(WIF1):c.288+8535G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,276 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.030 (153 hom., cov: 32)
• Consequence: WIF1 NM_007191.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.178

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIF1	NM_007191.5	c.288+8535G>A		intron_variant		ENST00000286574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIF1	ENST00000286574.9	c.288+8535G>A		intron_variant		1	NM_007191.5	P1
WIF1	ENST00000546001.1	c.102+8535G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4606 AN: 152158 Hom.: 151 Cov.: 32

Gnomad AFR AF: 0.0822

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00936

Gnomad OTH AF: 0.0306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0303 AC: 4612 AN: 152276 Hom.: 153 Cov.: 32 AF XY: 0.0303 AC XY: 2258 AN XY: 74466

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.0171

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00936

Gnomad4 OTH AF: 0.0303

Alfa AF: 0.0179 Hom.: 14

Bravo AF: 0.0329

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.3
Dann	Benign	0.68

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: rs10506532; hg19: chr12-65505662;