chr1-100738142-C-T

Variant names:

• chr1-100738142-C-T
• rs3176878
• NM_001078.4:c.2079C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001078.4(VCAM1):​c.2079C>T​(p.Asp693Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,612,012 control chromosomes in the GnomAD database, including 21,597 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 0.16 (2154 hom., cov: 32)
  • Exomes 𝑓: 0.16 (19443 hom.)
• Consequence: VCAM1 NM_001078.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 31 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=0.196 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.2079C>T	p.Asp693Asp	synonymous_variant	Exon 9 of 9	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.1893C>T	p.Asp631Asp	synonymous_variant	Exon 9 of 9		NP_001186763.1
VCAM1	NM_080682.3	c.1803C>T	p.Asp601Asp	synonymous_variant	Exon 8 of 8		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.2079C>T	p.Asp693Asp	synonymous_variant	Exon 9 of 9	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24478 AN: 151994 Hom.: 2153 Cov.: 32

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0870

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.176

GnomAD2 exomes AF: 0.162 AC: 40559 AN: 250800 AF XY: 0.156

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.0126

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.158 AC: 230393 AN: 1459900 Hom.: 19443 Cov.: 30 AF XY: 0.156 AC XY: 113170 AN XY: 726242

African (AFR) AF: 0.156 AC: 5216 AN: 33426

American (AMR) AF: 0.266 AC: 11897 AN: 44642

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 6875 AN: 26078

East Asian (EAS) AF: 0.00767 AC: 304 AN: 39630

South Asian (SAS) AF: 0.0931 AC: 8008 AN: 86056

European-Finnish (FIN) AF: 0.136 AC: 7251 AN: 53388

Middle Eastern (MID) AF: 0.132 AC: 749 AN: 5666

European-Non Finnish (NFE) AF: 0.163 AC: 180598 AN: 1110698

Other (OTH) AF: 0.157 AC: 9495 AN: 60316

GnomAD4 genome AF: 0.161 AC: 24484 AN: 152112 Hom.: 2154 Cov.: 32 AF XY: 0.157 AC XY: 11678 AN XY: 74378

African (AFR) AF: 0.157 AC: 6521 AN: 41514

American (AMR) AF: 0.232 AC: 3550 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3462

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5182

South Asian (SAS) AF: 0.0872 AC: 421 AN: 4826

European-Finnish (FIN) AF: 0.113 AC: 1192 AN: 10584

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11180 AN: 67940

Other (OTH) AF: 0.174 AC: 368 AN: 2116

Alfa AF: 0.168 Hom.: 4748

Bravo AF: 0.169

Asia WGS AF: 0.0610 AC: 212 AN: 3478

EpiCase AF: 0.166

EpiControl AF: 0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.2
DANN	Benign	0.30
PhyloP100		0.20
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: rs3176878; hg19: chr1-101203698; COSMIC: COSV108108889;