rs2358817

chr1-117148136-C-T

Variant summary

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

The NM_024626.4(VTCN1):c.725-354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,178 control chromosomes in the GnomAD database, including 3,739 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 (3739 hom., cov: 32)
• Consequence: VTCN1 NM_024626.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VTCN1	NM_024626.4	c.725-354G>A		intron_variant		ENST00000369458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VTCN1	ENST00000369458.8	c.725-354G>A		intron_variant		1	NM_024626.4	P1
VTCN1	ENST00000328189.7	c.377-354G>A		intron_variant		5
VTCN1	ENST00000359008.8	c.734-354G>A		intron_variant		5
VTCN1	ENST00000539893.5	c.440-354G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25539 AN: 152060 Hom.: 3722 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0971

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.168 AC: 25598 AN: 152178 Hom.: 3739 Cov.: 32 AF XY: 0.163 AC XY: 12123 AN XY: 74420

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.0971

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0775

Gnomad4 OTH AF: 0.153

Alfa AF: 0.0971 Hom.: 1103

Bravo AF: 0.181

Asia WGS AF: 0.146 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.4
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2358817; hg19: chr1-117690758;