chr1-100720511-A-G

Variant names:

• chr1-100720511-A-G
• NM_001078.4:c.100A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001078.4(VCAM1):​c.100A>G​(p.Arg34Gly) 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. 14/22 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: 1.96
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1707361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.100A>G	p.Arg34Gly	missense_variant	Exon 2 of 9	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.100A>G	p.Arg34Gly	missense_variant	Exon 2 of 9		NP_001186763.1
VCAM1	NM_080682.3	c.100A>G	p.Arg34Gly	missense_variant	Exon 2 of 8		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.100A>G	p.Arg34Gly	missense_variant	Exon 2 of 9	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 25, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.100A>G (p.R34G) alteration is located in exon 2 (coding exon 2) of the VCAM1 gene. This alteration results from a A to G substitution at nucleotide position 100, causing the arginine (R) at amino acid position 34 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.32	.;.;T;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.2	M;M;M;.
PhyloP100		2.0
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.3	N;D;N;D
REVEL	Benign	0.14
Sift	Benign	0.044	D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.23, 0.74	.;B;P;.
Vest4		0.21
MutPred		0.52		Gain of glycosylation at S33 (P = 0.0423);Gain of glycosylation at S33 (P = 0.0423);Gain of glycosylation at S33 (P = 0.0423);Gain of glycosylation at S33 (P = 0.0423);
MVP		0.46
MPC		0.32
ClinPred		0.31	T
GERP RS		5.8
Varity_R		0.37
gMVP		0.82
Mutation Taster		=79/21	polymorphism

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

hg19: chr1-101186067;