chr1-100725310-A-C

Position:

• chr1-100725310-A-C

Variant summary

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

The NM_001078.4(VCAM1):​c.928+420A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,680 control chromosomes in the GnomAD database, including 3,189 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 0.18 (3189 hom., cov: 31)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

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=-0.79).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAM1	NM_001078.4	c.928+420A>C		intron_variant		ENST00000294728.7
VCAM1	NM_001199834.2	c.742+420A>C		intron_variant
VCAM1	NM_080682.3	c.928+420A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7	c.928+420A>C		intron_variant		1	NM_001078.4	P1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27809 AN: 151562 Hom.: 3188 Cov.: 31

Gnomad AFR AF: 0.0473

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.183 AC: 27809 AN: 151680 Hom.: 3189 Cov.: 31 AF XY: 0.188 AC XY: 13948 AN XY: 74086

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.174

Alfa AF: 0.195 Hom.: 512

Bravo AF: 0.174

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.70

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: rs3917010; hg19: chr1-101190866;