chr1-117210906-G-A

Variant names:

• chr1-117210906-G-A
• rs3738414
• NM_024626.4:c.-51C>T

Variant summary

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

The NM_024626.4(VTCN1):​c.-51C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,600,222 control chromosomes in the GnomAD database, including 2,021 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 0.023 (221 hom., cov: 32)
  • Exomes 𝑓: 0.023 (1800 hom.)
• Consequence: VTCN1 NM_024626.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VTCN1	NM_024626.4	c.-51C>T		5_prime_UTR_variant	Exon 1 of 6	ENST00000369458.8	NP_078902.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VTCN1	ENST00000369458.8	c.-51C>T		5_prime_UTR_variant	Exon 1 of 6	1	NM_024626.4	ENSP00000358470.3
VTCN1	ENST00000328189.7	c.-51C>T		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000328168.3
VTCN1	ENST00000463461.5	n.22C>T		non_coding_transcript_exon_variant	Exon 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0227 AC: 3453 AN: 152164 Hom.: 221 Cov.: 32

Gnomad AFR AF: 0.00352

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.0380 AC: 9551 AN: 251048 Hom.: 824 AF XY: 0.0355 AC XY: 4814 AN XY: 135680

Gnomad AFR exome AF: 0.00363

Gnomad AMR exome AF: 0.0256

Gnomad ASJ exome AF: 0.0152

Gnomad EAS exome AF: 0.287

Gnomad SAS exome AF: 0.0104

Gnomad FIN exome AF: 0.0529

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.0268

GnomAD4 exome AF: 0.0226 AC: 32758 AN: 1447940 Hom.: 1800 Cov.: 27 AF XY: 0.0220 AC XY: 15869 AN XY: 721266

Gnomad4 AFR exome AF: 0.00295

Gnomad4 AMR exome AF: 0.0242

Gnomad4 ASJ exome AF: 0.0156

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.00974

Gnomad4 FIN exome AF: 0.0515

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.0311

GnomAD4 genome AF: 0.0227 AC: 3450 AN: 152282 Hom.: 221 Cov.: 32 AF XY: 0.0260 AC XY: 1939 AN XY: 74462

Gnomad4 AFR AF: 0.00351

Gnomad4 AMR AF: 0.0121

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.0533

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0139 Hom.: 47

Bravo AF: 0.0211

Asia WGS AF: 0.0990 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.5
DANN	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3738414; hg19: chr1-117753528; COSMIC: COSV60223375;