Genetic Variant VCAM1:p.Ile716Leu (chr1-100738209-A-T) – 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.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. 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 0.016 ( 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

Publications

16 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=0.0019263327).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001078.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCAM1	NM_001078.4	MANE Select	c.2146A>T	p.Ile716Leu	missense	Exon 9 of 9	NP_001069.1	P19320-1
VCAM1	NM_001199834.2		c.1960A>T	p.Ile654Leu	missense	Exon 9 of 9	NP_001186763.1	P19320-3
VCAM1	NM_080682.3		c.1870A>T	p.Ile624Leu	missense	Exon 8 of 8	NP_542413.1	P19320-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VCAM1	ENST00000294728.7	TSL:1 MANE Select	c.2146A>T	p.Ile716Leu	missense	Exon 9 of 9	ENSP00000294728.2	P19320-1
VCAM1	ENST00000347652.6	TSL:1	c.1870A>T	p.Ile624Leu	missense	Exon 8 of 8	ENSP00000304611.2	P19320-2
VCAM1	ENST00000855907.1		c.2050A>T	p.Ile684Leu	missense	Exon 9 of 9	ENSP00000525966.1

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

GnomAD2 exomes

AF:

0.00450

AC:

1130

AN:

251280

AF XY:

0.00327

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 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

African (AFR)

AF:

0.0575

AC:

1923

AN:

33462

American (AMR)

AF:

0.00344

AC:

154

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.000128

AC:

AN:

86234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000103

AC:

115

AN:

1111806

Other (OTH)

AF:

0.00399

AC:

241

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

125

249

374

498

623

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.0162

AC:

2474

AN:

152290

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1205

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0564

AC:

2343

AN:

41552

American (AMR)

AF:

0.00608

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67998

Other (OTH)

AF:

0.0109

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

120

239

359

478

598

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00468

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.092

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

1.7

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.44

REVEL

Benign

0.080

Sift

Uncertain

0.017

Sift4G

Benign

0.14

Polyphen

0.22

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

Mutation Taster

=93/7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over