rs3176879

Positions:

• chr1-100738271-G-A

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.2208G>A​(p.Lys736=) 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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=-0.6).
• BP6: Variant 1-100738271-G-A is Benign according to our data. Variant chr1-100738271-G-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.2208G>A	p.Lys736=	synonymous_variant	9/9	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.2022G>A	p.Lys674=	synonymous_variant	9/9		NP_001186763.1
VCAM1	NM_080682.3	c.1932G>A	p.Lys644=	synonymous_variant	8/8		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.2208G>A	p.Lys736=	synonymous_variant	9/9	1	NM_001078.4	ENSP00000294728	P1

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

GnomAD3 exomes AF: 0.941 AC: 235998 AN: 250764 Hom.: 111709 AF XY: 0.947 AC XY: 128363 AN XY: 135514

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 SAS exome AF: 0.964

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

Gnomad4 AFR exome AF: 0.706

Gnomad4 AMR exome AF: 0.965

Gnomad4 ASJ exome AF: 0.970

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.966

Gnomad4 FIN exome AF: 0.968

Gnomad4 NFE exome AF: 0.968

Gnomad4 OTH exome AF: 0.951

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

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.962

Gnomad4 FIN AF: 0.964

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.915

Alfa AF: 0.951 Hom.: 114052

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

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: rs3176879; hg19: chr1-101203827; COSMIC: COSV54119583;