Genetic Variant VCAM1:p.Gly413Ala (chr1-100731231-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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: 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

Publications

30 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VCAM1	NM_001078.4 link	c.1238G>C	p.Gly413Ala	missense_variant	Exon 6 of 9	ENST00000294728.7	NP_001069.1	P19320-1
VCAM1	NM_001199834.2 link	c.1052G>C	p.Gly351Ala	missense_variant	Exon 6 of 9		NP_001186763.1	P19320-3
VCAM1	NM_080682.3 link	c.962G>C	p.Gly321Ala	missense_variant	Exon 5 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.1238G>C	p.Gly413Ala	missense_variant	Exon 6 of 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

GnomAD2 exomes

AF:

0.00987

AC:

2469

AN:

250124

AF XY:

0.00718

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 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

African (AFR)

AF:

0.131

AC:

4366

AN:

33432

American (AMR)

AF:

0.00830

AC:

370

AN:

44568

Ashkenazi Jewish (ASJ)

AF:

0.000154

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.000360

AC:

AN:

86064

European-Finnish (FIN)

AF:

0.0000937

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000359

AC:

399

AN:

1111366

Other (OTH)

AF:

0.00865

AC:

522

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

268

536

803

1071

1339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0357

AC:

5436

AN:

152186

Hom.:

302

Cov.:

AF XY:

0.0346

AC XY:

2572

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.123

AC:

5126

AN:

41506

American (AMR)

AF:

0.0139

AC:

212

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000426

AC:

AN:

68008

Other (OTH)

AF:

0.0289

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

238

476

715

953

1191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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

PhyloP100

-0.071

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

Mutation Taster

=97/3

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over