rs12317641

Variant names:

• chr12-65055962-T-C
• rs12317641
• NM_007191.5:c.922+69A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-65055962-T-C
• chr12-65055962-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIF1	NM_007191.5	MANE Select	c.922+69A>G		intron	N/A	NP_009122.2	Q9Y5W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIF1	ENST00000286574.9	TSL:1 MANE Select	c.922+69A>G		intron	N/A	ENSP00000286574.4	Q9Y5W5
	WIF1	ENST00000954483.1		c.892+69A>G		intron	N/A	ENSP00000624542.1
	WIF1	ENST00000954485.1		c.892+69A>G		intron	N/A	ENSP00000624544.1

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

African (AFR) AF: 0.201 AC: 5770 AN: 28698

American (AMR) AF: 0.0154 AC: 604 AN: 39280

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 333 AN: 22986

East Asian (EAS) AF: 0.000546 AC: 21 AN: 38490

South Asian (SAS) AF: 0.0514 AC: 3882 AN: 75598

European-Finnish (FIN) AF: 0.00134 AC: 69 AN: 51416

Middle Eastern (MID) AF: 0.0362 AC: 190 AN: 5254

European-Non Finnish (NFE) AF: 0.00956 AC: 8859 AN: 926550

Other (OTH) AF: 0.0246 AC: 1297 AN: 52826

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

African (AFR) AF: 0.192 AC: 7965 AN: 41518

American (AMR) AF: 0.0269 AC: 411 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5188

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4824

European-Finnish (FIN) AF: 0.000942 AC: 10 AN: 10618

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00967 AC: 658 AN: 68034

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0316 Hom.: 224

Bravo AF: 0.0683

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.043
DANN	Benign	0.34
PhyloP100		-1.9
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: rs12317641; hg19: chr12-65449742;