rs10754339

Positions:

• chr1-117147650-G-A
• chr1-117147650-G-C

Variant summary

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

The NM_024626.4(VTCN1):​c.*8C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,611,228 control chromosomes in the GnomAD database, including 652,566 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 0.77 (49429 hom., cov: 32)
  • Exomes 𝑓: 0.91 (603137 hom.)
• Consequence: VTCN1 NM_024626.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.916 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VTCN1	NM_024626.4	c.*8C>T		3_prime_UTR_variant	5/6	ENST00000369458.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VTCN1	ENST00000369458.8	c.*8C>T		3_prime_UTR_variant	5/6	1	NM_024626.4	P1
VTCN1	ENST00000328189.7	c.*8C>T		3_prime_UTR_variant	4/5	5
VTCN1	ENST00000359008.8	c.*8C>T		3_prime_UTR_variant	5/6	5
VTCN1	ENST00000539893.5	c.*8C>T		3_prime_UTR_variant	5/6	2

Frequencies

GnomAD3 genomes AF: 0.770 AC: 117055 AN: 151968 Hom.: 49425 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.984

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.925

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.959

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.804

GnomAD3 exomes AF: 0.883 AC: 219361 AN: 248300 Hom.: 99314 AF XY: 0.891 AC XY: 119500 AN XY: 134154

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.930

Gnomad ASJ exome AF: 0.922

Gnomad EAS exome AF: 0.894

Gnomad SAS exome AF: 0.875

Gnomad FIN exome AF: 0.959

Gnomad NFE exome AF: 0.924

Gnomad OTH exome AF: 0.904

GnomAD4 exome AF: 0.905 AC: 1320573 AN: 1459142 Hom.: 603137 Cov.: 53 AF XY: 0.906 AC XY: 657601 AN XY: 725844

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.923

Gnomad4 ASJ exome AF: 0.923

Gnomad4 EAS exome AF: 0.889

Gnomad4 SAS exome AF: 0.879

Gnomad4 FIN exome AF: 0.960

Gnomad4 NFE exome AF: 0.921

Gnomad4 OTH exome AF: 0.880

GnomAD4 genome AF: 0.770 AC: 117078 AN: 152086 Hom.: 49429 Cov.: 32 AF XY: 0.777 AC XY: 57774 AN XY: 74344

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.876

Gnomad4 ASJ AF: 0.925

Gnomad4 EAS AF: 0.898

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.959

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.800

Alfa AF: 0.882 Hom.: 101815

Bravo AF: 0.748

Asia WGS AF: 0.828 AC: 2880 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	0.89
DANN	Benign	0.46

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10754339; hg19: chr1-117690272;