1-100737839-A-T

Position:

• chr1-100737839-A-T

Variant summary

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

The NM_001078.4(VCAM1):​c.2060-284A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 215,674 control chromosomes in the GnomAD database, including 35,316 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 (23218 hom., cov: 31)
  • Exomes 𝑓: 0.60 (12098 hom.)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAM1	NM_001078.4	c.2060-284A>T		intron_variant		ENST00000294728.7
VCAM1	NM_001199834.2	c.1874-284A>T		intron_variant
VCAM1	NM_080682.3	c.1784-284A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7	c.2060-284A>T		intron_variant		1	NM_001078.4	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80211 AN: 151762 Hom.: 23206 Cov.: 31

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.682

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.603 AC: 38464 AN: 63794 Hom.: 12098 Cov.: 3 AF XY: 0.599 AC XY: 19681 AN XY: 32860

Gnomad4 AFR exome AF: 0.307

Gnomad4 AMR exome AF: 0.473

Gnomad4 ASJ exome AF: 0.543

Gnomad4 EAS exome AF: 0.490

Gnomad4 SAS exome AF: 0.469

Gnomad4 FIN exome AF: 0.671

Gnomad4 NFE exome AF: 0.652

Gnomad4 OTH exome AF: 0.593

GnomAD4 genome AF: 0.528 AC: 80241 AN: 151880 Hom.: 23218 Cov.: 31 AF XY: 0.525 AC XY: 39012 AN XY: 74238

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.682

Gnomad4 NFE AF: 0.654

Gnomad4 OTH AF: 0.521

Alfa AF: 0.570 Hom.: 3151

Bravo AF: 0.505

Asia WGS AF: 0.522 AC: 1813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3176877; hg19: chr1-101203395;