12-65055291-A-G

Position:

• chr12-65055291-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.923-78T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,467,238 control chromosomes in the GnomAD database, including 43,632 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3299 hom., cov: 33)
  • Exomes 𝑓: 0.24 (40333 hom.)
• Consequence: WIF1 NM_007191.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.300

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=-0.89).
• BP6: Variant 12-65055291-A-G is Benign according to our data. Variant chr12-65055291-A-G is described in ClinVar as [Benign]. Clinvar id is 1266554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WIF1	NM_007191.5	c.923-78T>C		intron_variant		ENST00000286574.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WIF1	ENST00000286574.9	c.923-78T>C		intron_variant		1	NM_007191.5	P1
WIF1	ENST00000543094.1	c.170-78T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30165 AN: 152008 Hom.: 3298 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.240 AC: 315827 AN: 1315112 Hom.: 40333 AF XY: 0.238 AC XY: 155078 AN XY: 651696

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.000850

Gnomad4 SAS exome AF: 0.144

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.262

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.198 AC: 30170 AN: 152126 Hom.: 3299 Cov.: 33 AF XY: 0.194 AC XY: 14392 AN XY: 74376

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.189

Alfa AF: 0.214 Hom.: 480

Bravo AF: 0.198

Asia WGS AF: 0.0640 AC: 226 AN: 3478

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 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.80

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: rs1026025; hg19: chr12-65449071;