NM_001078.4:c.25C>G

Variant names:

• chr1-100719885-C-G
• rs1659891136
• NM_001078.4:c.25C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001078.4(VCAM1):​c.25C>G​(p.Leu9Val) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L9F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VCAM1 NM_001078.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02742982).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.25C>G	p.Leu9Val	missense_variant	Exon 1 of 9	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.25C>G	p.Leu9Val	missense_variant	Exon 1 of 9		NP_001186763.1
VCAM1	NM_080682.3	c.25C>G	p.Leu9Val	missense_variant	Exon 1 of 8		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.25C>G	p.Leu9Val	missense_variant	Exon 1 of 9	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.3
DANN	Benign	0.63
DEOGEN2	Benign	0.088	.;.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.42	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.027	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.46	N;N;N;.
PhyloP100		0.25
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.21	N;N;N;N
REVEL	Benign	0.017
Sift	Benign	0.24	T;T;T;T
Sift4G	Benign	0.79	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.061
MutPred		0.39		Gain of methylation at K4 (P = 0.0583);Gain of methylation at K4 (P = 0.0583);Gain of methylation at K4 (P = 0.0583);Gain of methylation at K4 (P = 0.0583);
MVP		0.22
MPC		0.16
ClinPred		0.023	T
GERP RS		1.4
PromoterAI		0.12	Neutral
Varity_R		0.023
gMVP		0.32
Mutation Taster		=93/7	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

dbSNP: rs1659891136; hg19: chr1-101185441;