Variant rs3783615 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001078.4(VCAM1):c.2146A>T(p.Ile716Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00306 in 1,613,854 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.016 ( 80 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 66 hom. )

Consequence

VCAM1
NM_001078.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.75

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019263327).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
VCAM1	NM_001078.4 linkuse as main transcript	c.2146A>T	p.Ile716Leu	missense_variant	9/9	ENST00000294728.7
VCAM1	NM_001199834.2 linkuse as main transcript	c.1960A>T	p.Ile654Leu	missense_variant	9/9
VCAM1	NM_080682.3 linkuse as main transcript	c.1870A>T	p.Ile624Leu	missense_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7 linkuse as main transcript	c.2146A>T	p.Ile716Leu	missense_variant	9/9	1	NM_001078.4	P1	P19320-1

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2471

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00450

AC:

1130

AN:

251280

Hom.:

AF XY:

0.00327

AC XY:

444

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.0603

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00168

AC:

2462

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1040

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.0575

Gnomad4 AMR exome

AF:

0.00344

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00399

GnomAD4 genome

AF:

0.0162

AC:

2474

AN:

152290

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1205

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0564

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00468

Hom.:

Bravo

AF:

0.0186

ESP6500AA

AF:

0.0538

AC:

237

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00542

AC:

658

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.67

T;T;T;T

MetaRNN

Benign

0.0019

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.86

N;N;N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.44

N;N;N;N

REVEL

Benign

0.080

Sift

Uncertain

0.017

D;D;D;T

Sift4G

Benign

0.14

T;D;T;D

Polyphen

0.22, 0.038

.;B;B;.

Vest4

0.18

MutPred

0.37

.;.;Loss of MoRF binding (P = 0.1388);.;

MVP

0.33

MPC

0.24

ClinPred

0.018

GERP RS

4.8

Varity_R

0.13

gMVP

0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over