chr1-100723854-C-T

Position:

• chr1-100723854-C-T

Variant summary

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

The NM_001078.4(VCAM1):​c.661+514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0816 in 151,936 control chromosomes in the GnomAD database, including 542 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 0.082 (542 hom., cov: 32)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.661+514C>T		intron_variant		ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.475+514C>T		intron_variant			NP_001186763.1
VCAM1	NM_080682.3	c.661+514C>T		intron_variant			NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.661+514C>T		intron_variant		1	NM_001078.4	ENSP00000294728	P1

Frequencies

GnomAD3 genomes AF: 0.0816 AC: 12393 AN: 151818 Hom.: 541 Cov.: 32

Gnomad AFR AF: 0.0590

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0749

Gnomad ASJ AF: 0.0698

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.0417

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0937

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0816 AC: 12403 AN: 151936 Hom.: 542 Cov.: 32 AF XY: 0.0830 AC XY: 6164 AN XY: 74242

Gnomad4 AFR AF: 0.0590

Gnomad4 AMR AF: 0.0751

Gnomad4 ASJ AF: 0.0698

Gnomad4 EAS AF: 0.0389

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0937

Gnomad4 OTH AF: 0.0785

Alfa AF: 0.0870 Hom.: 555

Bravo AF: 0.0756

Asia WGS AF: 0.0420 AC: 145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.079
DANN	Benign	0.53

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: rs3917009; hg19: chr1-101189410;