Genetic Variant VCAM1:p.Gly10Glu (chr1-100719889-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_001078.4(VCAM1):c.29G>A(p.Gly10Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,350 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

VCAM1
NM_001078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.684

Publications

0 publications found

Variant links:

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]

VCAM1 links:

ENSG00000299357 (HGNC:):

ENSG00000299357 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4 link	c.29G>A	p.Gly10Glu	missense_variant	Exon 1 of 9	ENST00000294728.7	NP_001069.1	P19320-1
VCAM1	NM_001199834.2 link	c.29G>A	p.Gly10Glu	missense_variant	Exon 1 of 9		NP_001186763.1	P19320-3
VCAM1	NM_080682.3 link	c.29G>A	p.Gly10Glu	missense_variant	Exon 1 of 8		NP_542413.1	P19320-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7 link	c.29G>A	p.Gly10Glu	missense_variant	Exon 1 of 9	1	NM_001078.4	ENSP00000294728.2		P19320-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459350

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725970

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33366

American (AMR)

AF:

0.00

AC:

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26028

East Asian (EAS)

AF:

0.00

AC:

AN:

39656

South Asian (SAS)

AF:

0.00

AC:

AN:

86004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53364

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1110356

Other (OTH)

AF:

0.00

AC:

AN:

60216

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.29G>A (p.G10E) alteration is located in exon 1 (coding exon 1) of the VCAM1 gene. This alteration results from a G to A substitution at nucleotide position 29, causing the glycine (G) at amino acid position 10 to be replaced by a glutamic acid (E). 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

0.33

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;.;T;T

Eigen

Benign

0.077

Eigen_PC

Benign

0.014

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.86

D;D;D;D

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.63

D;D;D;D

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.5

M;M;M;.

PhyloP100

0.68

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.010

D;T;T;T

Sift4G

Benign

0.14

T;T;T;T

Polyphen

1.0, 0.89

.;D;P;.

Vest4

0.40

MutPred

0.71

Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);

MVP

0.93

MPC

0.62

ClinPred

0.72

GERP RS

3.3

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.046

gMVP

0.52

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over