rs2051047

Positions:

• chr1-117153415-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024626.4(VTCN1):​c.446-46C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,555,558 control chromosomes in the GnomAD database, including 19,742 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 0.23 (8185 hom., cov: 31)
  • Exomes 𝑓: 0.095 (11557 hom.)
• Consequence: VTCN1 NM_024626.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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]

VTCN1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VTCN1	NM_024626.4	c.446-46C>T		intron_variant		ENST00000369458.8	NP_078902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VTCN1	ENST00000369458.8	c.446-46C>T		intron_variant		1	NM_024626.4	ENSP00000358470.3

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34505 AN: 151454 Hom.: 8147 Cov.: 31

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.0969

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0409

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0784

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.121 AC: 25307 AN: 209030 Hom.: 3681 AF XY: 0.114 AC XY: 12787 AN XY: 112302

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.0713

Gnomad ASJ exome AF: 0.0794

Gnomad EAS exome AF: 0.102

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.0421

Gnomad NFE exome AF: 0.0763

Gnomad OTH exome AF: 0.0942

GnomAD4 exome AF: 0.0949 AC: 133270 AN: 1403998 Hom.: 11557 Cov.: 31 AF XY: 0.0944 AC XY: 65316 AN XY: 691902

Gnomad4 AFR exome AF: 0.627

Gnomad4 AMR exome AF: 0.0774

Gnomad4 ASJ exome AF: 0.0765

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.128

Gnomad4 FIN exome AF: 0.0400

Gnomad4 NFE exome AF: 0.0788

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.228 AC: 34599 AN: 151560 Hom.: 8185 Cov.: 31 AF XY: 0.222 AC XY: 16403 AN XY: 74006

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0750

Gnomad4 EAS AF: 0.0967

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0409

Gnomad4 NFE AF: 0.0784

Gnomad4 OTH AF: 0.198

Alfa AF: 0.130 Hom.: 2126

Bravo AF: 0.250

Asia WGS AF: 0.162 AC: 563 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2051047; hg19: chr1-117696037;