rs3181092

Positions:

• chr1-100739088-A-G

Variant summary

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

The 1-100739088-A-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 152,072 control chromosomes in the GnomAD database, including 23,535 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 0.53 (23535 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: VCAM1 NM_001078.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

Genes affected

VCAM1 (HGNC:12663): (vascular cell adhesion molecule 1) This gene is a member of the Ig superfamily and encodes a cell surface sialoglycoprotein expressed by cytokine-activated endothelium. This type I membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of artherosclerosis and rheumatoid arthritis. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAM1	NM_001078.4			downstream_gene_variant		ENST00000294728.7
VCAM1	NM_001199834.2			downstream_gene_variant
VCAM1	NM_080682.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7			downstream_gene_variant		1	NM_001078.4	P1
VCAM1	ENST00000347652.6			downstream_gene_variant		1
VCAM1	ENST00000370115.1			downstream_gene_variant		5
VCAM1	ENST00000603679.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80568 AN: 151954 Hom.: 23525 Cov.: 33

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.519

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.530 AC: 80603 AN: 152072 Hom.: 23535 Cov.: 33 AF XY: 0.528 AC XY: 39220 AN XY: 74336

Gnomad4 AFR AF: 0.286

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.538

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.661

Gnomad4 OTH AF: 0.524

Alfa AF: 0.553 Hom.: 5956

Bravo AF: 0.506

Asia WGS AF: 0.532 AC: 1850 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.031
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3181092; hg19: chr1-101204644;