NM_001078.4:c.599A>C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001078.4(VCAM1):c.599A>C(p.His200Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
VCAM1
NM_001078.4 missense
NM_001078.4 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: 0.353
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]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
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=0.18403447).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| VCAM1 | NM_001078.4 | c.599A>C | p.His200Pro | missense_variant | Exon 3 of 9 | ENST00000294728.7 | NP_001069.1 | |
| VCAM1 | NM_001199834.2 | c.413A>C | p.His138Pro | missense_variant | Exon 3 of 9 | NP_001186763.1 | ||
| VCAM1 | NM_080682.3 | c.599A>C | p.His200Pro | missense_variant | Exon 3 of 8 | NP_542413.1 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152074
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460932Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726812 show subpopulations
GnomAD4 exome
AF:
AC:
2
AN:
1460932
Hom.:
Cov.:
31
AF XY:
AC XY:
2
AN XY:
726812
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33414
American (AMR)
AF:
AC:
0
AN:
44638
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26092
East Asian (EAS)
AF:
AC:
0
AN:
39690
South Asian (SAS)
AF:
AC:
0
AN:
86232
European-Finnish (FIN)
AF:
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111376
Other (OTH)
AF:
AC:
0
AN:
60326
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.00000658 AC: 1AN: 152074Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74276 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152074
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74276
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41438
American (AMR)
AF:
AC:
0
AN:
15250
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3466
East Asian (EAS)
AF:
AC:
0
AN:
5166
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67984
Other (OTH)
AF:
AC:
0
AN:
2088
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Dec 06, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.599A>C (p.H200P) alteration is located in exon 3 (coding exon 3) of the VCAM1 gene. This alteration results from a A to C substitution at nucleotide position 599, causing the histidine (H) at amino acid position 200 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
DANN
Benign
DEOGEN2
Benign
.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;L;.
PhyloP100
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.0
.;B;B;.
Vest4
MutPred
0.71
.;Loss of catalytic residue at D202 (P = 0.1169);Loss of catalytic residue at D202 (P = 0.1169);Loss of catalytic residue at D202 (P = 0.1169);
MVP
MPC
0.25
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.