rs12046117

Variant names:

• chr1-117208743-C-T
• rs12046117
• NM_024626.4:c.32+2081G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024626.4(VTCN1):​c.32+2081G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,130 control chromosomes in the GnomAD database, including 2,222 homozygotes. 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: 𝑓 0.17 (2222 hom., cov: 32)
• Consequence: VTCN1 NM_024626.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.36
• Publications: 17 publications found

Genes affected

VTCN1 (HGNC:28873): (V-set domain containing T cell activation inhibitor 1) This gene encodes a protein belonging to the B7 costimulatory protein family. Proteins in this family are present on the surface of antigen-presenting cells and interact with ligand bound to receptors on the surface of T cells. Studies have shown that high levels of the encoded protein has been correlated with tumor progression. A pseudogene of this gene is located on chromosome 20. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTCN1	NM_024626.4	c.32+2081G>A		intron_variant	Intron 1 of 5	ENST00000369458.8	NP_078902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTCN1	ENST00000369458.8	c.32+2081G>A		intron_variant	Intron 1 of 5	1	NM_024626.4	ENSP00000358470.3
VTCN1	ENST00000328189.7	c.32+2081G>A		intron_variant	Intron 1 of 4	5		ENSP00000328168.3
VTCN1	ENST00000463461.5	n.104+2081G>A		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25119 AN: 152012 Hom.: 2215 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.210

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.170

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

GnomAD4 genome AF: 0.165 AC: 25148 AN: 152130 Hom.: 2222 Cov.: 32 AF XY: 0.165 AC XY: 12266 AN XY: 74350

African (AFR) AF: 0.222 AC: 9219 AN: 41488

American (AMR) AF: 0.134 AC: 2047 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3472

East Asian (EAS) AF: 0.283 AC: 1462 AN: 5168

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4818

European-Finnish (FIN) AF: 0.108 AC: 1142 AN: 10586

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.131 AC: 8910 AN: 68006

Other (OTH) AF: 0.168 AC: 354 AN: 2106

Alfa AF: 0.148 Hom.: 5432

Bravo AF: 0.167

Asia WGS AF: 0.253 AC: 879 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.013
DANN	Benign	0.29
PhyloP100		-4.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12046117; hg19: chr1-117751365;