chr1-100737839-A-T

Variant names:

• chr1-100737839-A-T
• rs3176877
• NM_001078.4:c.2060-284A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ENSG00000299357 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.2060-284A>T		intron_variant	Intron 8 of 8	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.1874-284A>T		intron_variant	Intron 8 of 8		NP_001186763.1
VCAM1	NM_080682.3	c.1784-284A>T		intron_variant	Intron 7 of 7		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.2060-284A>T		intron_variant	Intron 8 of 8	1	NM_001078.4	ENSP00000294728.2

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

African (AFR) AF: 0.307 AC: 625 AN: 2034

American (AMR) AF: 0.473 AC: 1177 AN: 2486

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1228 AN: 2262

East Asian (EAS) AF: 0.490 AC: 2113 AN: 4310

South Asian (SAS) AF: 0.469 AC: 2168 AN: 4620

European-Finnish (FIN) AF: 0.671 AC: 2057 AN: 3064

Middle Eastern (MID) AF: 0.565 AC: 182 AN: 322

European-Non Finnish (NFE) AF: 0.652 AC: 26633 AN: 40850

Other (OTH) AF: 0.593 AC: 2281 AN: 3846

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

African (AFR) AF: 0.295 AC: 12221 AN: 41404

American (AMR) AF: 0.510 AC: 7773 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1741 AN: 3466

East Asian (EAS) AF: 0.494 AC: 2553 AN: 5164

South Asian (SAS) AF: 0.512 AC: 2468 AN: 4822

European-Finnish (FIN) AF: 0.682 AC: 7201 AN: 10566

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44401 AN: 67888

Other (OTH) AF: 0.521 AC: 1100 AN: 2110

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
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3176877; hg19: chr1-101203395;