1-100723136-C-G

Position:

• chr1-100723136-C-G

Variant summary

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

The NM_001078.4(VCAM1):​c.457C>G​(p.Leu153Val) 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VCAM1 NM_001078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26

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=0.13894096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.457C>G	p.Leu153Val	missense_variant	3/9	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.271C>G	p.Leu91Val	missense_variant	3/9		NP_001186763.1
VCAM1	NM_080682.3	c.457C>G	p.Leu153Val	missense_variant	3/8		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.457C>G	p.Leu153Val	missense_variant	3/9	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.457C>G (p.L153V) alteration is located in exon 3 (coding exon 3) of the VCAM1 gene. This alteration results from a C to G substitution at nucleotide position 457, causing the leucine (L) at amino acid position 153 to be replaced by a valine (V). 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	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.4
DANN	Benign	0.88
DEOGEN2	Benign	0.095	.;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.84	T;D;T;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	.;M;M;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.88	N;N;N;N
REVEL	Benign	0.040
Sift	Uncertain	0.020	D;T;T;T
Sift4G	Uncertain	0.026	D;D;T;D
Polyphen		0.23, 0.37	.;B;B;.
Vest4		0.20
MutPred		0.49		.;Gain of methylation at K154 (P = 0.0311);Gain of methylation at K154 (P = 0.0311);Gain of methylation at K154 (P = 0.0311);
MVP		0.41
MPC		0.33
ClinPred		0.13	T
GERP RS		-0.97
Varity_R		0.26
gMVP		0.59

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: chr1-101188692;