Variant 1-100731231-G-C 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.1238G>C(p.Gly413Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00694 in 1,612,820 control chromosomes in the GnomAD database, including 616 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 0.036 ( 302 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 314 hom. )

Consequence

VCAM1
NM_001078.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0710

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=0.0018598735).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VCAM1	NM_001078.4 linkuse as main transcript	c.1238G>C	p.Gly413Ala	missense_variant	6/9	ENST00000294728.7	NP_001069.1	P19320-1
VCAM1	NM_001199834.2 linkuse as main transcript	c.1052G>C	p.Gly351Ala	missense_variant	6/9		NP_001186763.1	P19320-3
VCAM1	NM_080682.3 linkuse as main transcript	c.962G>C	p.Gly321Ala	missense_variant	5/8		NP_542413.1	P19320-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7 linkuse as main transcript	c.1238G>C	p.Gly413Ala	missense_variant	6/9	1	NM_001078.4	ENSP00000294728.2		P19320-1

Frequencies

GnomAD3 genomes

AF:

0.0356

AC:

5410

AN:

152068

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0140

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.00987

AC:

2469

AN:

250124

Hom.:

141

AF XY:

0.00718

AC XY:

971

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.00825

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000362

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000530

Gnomad OTH exome

AF:

0.00639

GnomAD4 exome

AF:

0.00394

AC:

5755

AN:

1460634

Hom.:

314

Cov.:

AF XY:

0.00348

AC XY:

2531

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.00830

Gnomad4 ASJ exome

AF:

0.000154

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000360

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.000359

Gnomad4 OTH exome

AF:

0.00865

GnomAD4 genome

AF:

0.0357

AC:

5436

AN:

152186

Hom.:

302

Cov.:

AF XY:

0.0346

AC XY:

2572

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.0139

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.0414

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.125

AC:

550

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0120

AC:

1461

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.000546

EpiControl

AF:

0.000831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.74

CADD

Benign

2.6

DANN

Benign

0.69

DEOGEN2

Benign

0.14

.;.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.83

T;T;T

MetaRNN

Benign

0.0019

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

.;.;M

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.4

N;N;N

REVEL

Benign

0.069

Sift

Benign

0.065

T;T;T

Sift4G

Benign

0.13

T;T;T

Polyphen

0.74, 0.97

.;P;D

Vest4

0.26

MPC

0.30

ClinPred

0.018

GERP RS

2.1

Varity_R

0.069

gMVP

0.52

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