1-100738142-C-T

Position:

• chr1-100738142-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001078.4(VCAM1):​c.2079C>T​(p.Asp693=) 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-100738142-C-T is Benign according to our data. Variant chr1-100738142-C-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
VCAM1	NM_001078.4	c.2079C>T	p.Asp693=	synonymous_variant	9/9	ENST00000294728.7
VCAM1	NM_001199834.2	c.1893C>T	p.Asp631=	synonymous_variant	9/9
VCAM1	NM_080682.3	c.1803C>T	p.Asp601=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7	c.2079C>T	p.Asp693=	synonymous_variant	9/9	1	NM_001078.4	P1

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

GnomAD3 exomes AF: 0.162 AC: 40559 AN: 250800 Hom.: 3916 AF XY: 0.156 AC XY: 21077 AN XY: 135532

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 SAS exome AF: 0.0919

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

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.266

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.00767

Gnomad4 SAS exome AF: 0.0931

Gnomad4 FIN exome AF: 0.136

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.157

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

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.232

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.0129

Gnomad4 SAS AF: 0.0872

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.165

Gnomad4 OTH AF: 0.174

Alfa AF: 0.169 Hom.: 3713

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

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: rs3176878; hg19: chr1-101203698;