1-100720641-C-T

Variant names:

• chr1-100720641-C-T
• NM_001078.4:c.230C>T

Variant summary

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

The NM_001078.4(VCAM1):​c.230C>T​(p.Thr77Ile) 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. 16/21 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: -1.31

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=0.09434548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.230C>T	p.Thr77Ile	missense_variant	Exon 2 of 9	ENST00000294728.7	NP_001069.1
VCAM1	NM_080682.3	c.230C>T	p.Thr77Ile	missense_variant	Exon 2 of 8		NP_542413.1
VCAM1	NM_001199834.2	c.154+76C>T		intron_variant	Intron 2 of 8		NP_001186763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.230C>T	p.Thr77Ile	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

Dec 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.230C>T (p.T77I) alteration is located in exon 2 (coding exon 2) of the VCAM1 gene. This alteration results from a C to T substitution at nucleotide position 230, causing the threonine (T) at amino acid position 77 to be replaced by an isoleucine (I). 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	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.31
DANN	Benign	0.96
DEOGEN2	Benign	0.17	.;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.58	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.073
Sift	Benign	0.070	T;D;T
Sift4G	Uncertain	0.020	D;D;D
Polyphen		0.020	B;P;.
Vest4		0.10
MutPred		0.60		Loss of glycosylation at T77 (P = 0.0243);Loss of glycosylation at T77 (P = 0.0243);Loss of glycosylation at T77 (P = 0.0243);
MVP		0.48
MPC		0.25
ClinPred		0.034	T
GERP RS		-2.6
Varity_R		0.21
gMVP		0.34

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: chr1-101186197; COSMIC: COSV54121698;