12-65055291-A-C

Variant names:

• chr12-65055291-A-C
• rs1026025
• NM_007191.5:c.923-78T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007191.5(WIF1):​c.923-78T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: WIF1 NM_007191.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.923-78T>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.923-78T>G		intron	N/A	ENSP00000286574.4	Q9Y5W5
	WIF1	ENST00000954483.1		c.893-78T>G		intron	N/A	ENSP00000624542.1
	WIF1	ENST00000954485.1		c.893-78T>G		intron	N/A	ENSP00000624544.1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.80
PhyloP100		0.30

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: rs1026025; hg19: chr12-65449071;