rs10506532

Variant names:

• chr12-65111882-C-T
• rs10506532
• NM_007191.5:c.288+8535G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 rank	MANE	Protein	UniProt
WIF1	NM_007191.5	c.288+8535G>A		intron_variant	Intron 2 of 9	ENST00000286574.9	NP_009122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIF1	ENST00000286574.9	c.288+8535G>A		intron_variant	Intron 2 of 9	1	NM_007191.5	ENSP00000286574.4
WIF1	ENST00000546001.1	c.102+8535G>A		intron_variant	Intron 1 of 3	5		ENSP00000442063.1

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

African (AFR) AF: 0.0822 AC: 3414 AN: 41530

American (AMR) AF: 0.0171 AC: 261 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5190

South Asian (SAS) AF: 0.0300 AC: 145 AN: 4828

European-Finnish (FIN) AF: 0.000848 AC: 9 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00936 AC: 637 AN: 68026

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.0195 Hom.: 15

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
PhyloP100		0.18
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: rs10506532; hg19: chr12-65505662;