chr1-100724864-G-A

Position:

• chr1-100724864-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001078.4(VCAM1):​c.902G>A​(p.Arg301Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VCAM1 NM_001078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.718

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09197369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAM1	NM_001078.4	c.902G>A	p.Arg301Lys	missense_variant	4/9	ENST00000294728.7
VCAM1	NM_001199834.2	c.716G>A	p.Arg239Lys	missense_variant	4/9
VCAM1	NM_080682.3	c.902G>A	p.Arg301Lys	missense_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7	c.902G>A	p.Arg301Lys	missense_variant	4/9	1	NM_001078.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.902G>A (p.R301K) alteration is located in exon 4 (coding exon 4) of the VCAM1 gene. This alteration results from a G to A substitution at nucleotide position 902, causing the arginine (R) at amino acid position 301 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.80
DEOGEN2	Benign	0.057	.;.;T;T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	T;T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.092	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.47	.;N;N;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.55	N;N;N;N
REVEL	Benign	0.016
Sift	Benign	0.82	T;T;T;T
Sift4G	Benign	0.74	T;T;T;T
Polyphen		0.16, 0.0010	.;B;B;.
Vest4		0.11
MutPred		0.41		.;Gain of ubiquitination at R301 (P = 0.0337);Gain of ubiquitination at R301 (P = 0.0337);Gain of ubiquitination at R301 (P = 0.0337);
MVP		0.46
MPC		0.16
ClinPred		0.045	T
GERP RS		2.4
Varity_R		0.046
gMVP		0.45

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-101190420;