chr12-65066588-A-G

Position:

• chr12-65066588-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007191.5(WIF1):​c.730+53T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 1,470,602 control chromosomes in the GnomAD database, including 294,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24889 hom., cov: 33)
  • Exomes 𝑓: 0.64 (269817 hom.)
• Consequence: WIF1 NM_007191.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.458

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 12-65066588-A-G is Benign according to our data. Variant chr12-65066588-A-G is described in ClinVar as [Benign]. Clinvar id is 1287191.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIF1	NM_007191.5	c.730+53T>C		intron_variant		ENST00000286574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIF1	ENST00000286574.9	c.730+53T>C		intron_variant		1	NM_007191.5	P1
WIF1	ENST00000543094.1	c.19+53T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83506 AN: 151952 Hom.: 24887 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.627

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.612

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.602

GnomAD4 exome AF: 0.637 AC: 839403 AN: 1318530 Hom.: 269817 AF XY: 0.637 AC XY: 418072 AN XY: 656716

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.567

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.721

Gnomad4 SAS exome AF: 0.609

Gnomad4 FIN exome AF: 0.692

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.635

GnomAD4 genome AF: 0.549 AC: 83540 AN: 152072 Hom.: 24889 Cov.: 33 AF XY: 0.555 AC XY: 41225 AN XY: 74334

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.697

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.600

Alfa AF: 0.581 Hom.: 3954

Bravo AF: 0.531

Asia WGS AF: 0.657 AC: 2278 AN: 3476

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	clinical testing	GeneDx	May 16, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.81

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: rs3782498; hg19: chr12-65460368;