rs7301320

Positions:

• chr12-65120486-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_007191.5(WIF1):​c.219A>G​(p.Ala73=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 1,613,906 control chromosomes in the GnomAD database, including 457,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44112 hom., cov: 32)
  • Exomes 𝑓: 0.75 (413389 hom.)
• Consequence: WIF1 NM_007191.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.09

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 12-65120486-T-C is Benign according to our data. Variant chr12-65120486-T-C is described in ClinVar as [Benign]. Clinvar id is 1269441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIF1	NM_007191.5	c.219A>G	p.Ala73=	synonymous_variant	2/10	ENST00000286574.9	NP_009122.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIF1	ENST00000286574.9	c.219A>G	p.Ala73=	synonymous_variant	2/10	1	NM_007191.5	ENSP00000286574	P1
WIF1	ENST00000546001.1	c.33A>G	p.Ala11=	synonymous_variant	1/4	5		ENSP00000442063

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115632 AN: 152062 Hom.: 44073 Cov.: 32

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.782

GnomAD3 exomes AF: 0.776 AC: 194925 AN: 251322 Hom.: 76437 AF XY: 0.780 AC XY: 106005 AN XY: 135836

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.713

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.999

Gnomad SAS exome AF: 0.846

Gnomad FIN exome AF: 0.759

Gnomad NFE exome AF: 0.743

Gnomad OTH exome AF: 0.775

GnomAD4 exome AF: 0.750 AC: 1096337 AN: 1461726 Hom.: 413389 Cov.: 51 AF XY: 0.753 AC XY: 547414 AN XY: 727156

Gnomad4 AFR exome AF: 0.768

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.781

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.842

Gnomad4 FIN exome AF: 0.753

Gnomad4 NFE exome AF: 0.733

Gnomad4 OTH exome AF: 0.768

GnomAD4 genome AF: 0.760 AC: 115726 AN: 152180 Hom.: 44112 Cov.: 32 AF XY: 0.766 AC XY: 56966 AN XY: 74390

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.725

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.857

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.784

Alfa AF: 0.750 Hom.: 54864

Bravo AF: 0.756

Asia WGS AF: 0.920 AC: 3196 AN: 3478

EpiCase AF: 0.757

EpiControl AF: 0.771

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.4
DANN	Benign	0.49

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: rs7301320; hg19: chr12-65514266;