NM_001078.4:c.2208G>A

Variant names:

• chr1-100738271-G-A
• rs3176879
• NM_001078.4:c.2208G>A

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.2208G>A​(p.Lys736Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 1,613,012 control chromosomes in the GnomAD database, including 732,484 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 0.89 (61494 hom., cov: 33)
  • Exomes 𝑓: 0.96 (670990 hom.)
• Consequence: VCAM1 NM_001078.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.885
• Publications: 35 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=-0.6).
• BP7: Synonymous conserved (PhyloP=0.885 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.2208G>A	p.Lys736Lys	synonymous_variant	Exon 9 of 9	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.2022G>A	p.Lys674Lys	synonymous_variant	Exon 9 of 9		NP_001186763.1
VCAM1	NM_080682.3	c.1932G>A	p.Lys644Lys	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.2208G>A	p.Lys736Lys	synonymous_variant	Exon 9 of 9	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135678 AN: 152048 Hom.: 61469 Cov.: 33

Gnomad AFR AF: 0.717

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.914

GnomAD2 exomes AF: 0.941 AC: 235998 AN: 250764 AF XY: 0.947

Gnomad AFR exome AF: 0.709

Gnomad AMR exome AF: 0.965

Gnomad ASJ exome AF: 0.968

Gnomad EAS exome AF: 0.834

Gnomad FIN exome AF: 0.966

Gnomad NFE exome AF: 0.970

Gnomad OTH exome AF: 0.960

GnomAD4 exome AF: 0.957 AC: 1398433 AN: 1460846 Hom.: 670990 Cov.: 45 AF XY: 0.958 AC XY: 696552 AN XY: 726718

African (AFR) AF: 0.706 AC: 23621 AN: 33436

American (AMR) AF: 0.965 AC: 43091 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 25313 AN: 26098

East Asian (EAS) AF: 0.816 AC: 32348 AN: 39626

South Asian (SAS) AF: 0.966 AC: 83154 AN: 86072

European-Finnish (FIN) AF: 0.968 AC: 51677 AN: 53396

Middle Eastern (MID) AF: 0.968 AC: 5575 AN: 5760

European-Non Finnish (NFE) AF: 0.968 AC: 1076254 AN: 1111440

Other (OTH) AF: 0.951 AC: 57400 AN: 60346

GnomAD4 genome AF: 0.892 AC: 135750 AN: 152166 Hom.: 61494 Cov.: 33 AF XY: 0.893 AC XY: 66464 AN XY: 74412

African (AFR) AF: 0.717 AC: 29721 AN: 41462

American (AMR) AF: 0.951 AC: 14550 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3352 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4289 AN: 5166

South Asian (SAS) AF: 0.962 AC: 4640 AN: 4824

European-Finnish (FIN) AF: 0.964 AC: 10245 AN: 10624

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65827 AN: 67994

Other (OTH) AF: 0.915 AC: 1932 AN: 2112

Alfa AF: 0.944 Hom.: 146252

Bravo AF: 0.881

Asia WGS AF: 0.918 AC: 3192 AN: 3478

EpiCase AF: 0.968

EpiControl AF: 0.970

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.4
DANN	Benign	0.49
PhyloP100		0.89
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: rs3176879; hg19: chr1-101203827; COSMIC: COSV54119583;