Genetic Variant VCAM1:c.2060-284A>T (chr1-100737839-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.2060-284A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 215,674 control chromosomes in the GnomAD database, including 35,316 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 23218 hom., cov: 31)

Exomes 𝑓: 0.60 ( 12098 hom. )

Consequence

VCAM1
NM_001078.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.09

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4 link	c.2060-284A>T	intron_variant	Intron 8 of 8	ENST00000294728.7	NP_001069.1	P19320-1
VCAM1	NM_001199834.2 link	c.1874-284A>T	intron_variant	Intron 8 of 8		NP_001186763.1	P19320-3
VCAM1	NM_080682.3 link	c.1784-284A>T	intron_variant	Intron 7 of 7		NP_542413.1	P19320-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7 link	c.2060-284A>T		intron_variant	Intron 8 of 8	1	NM_001078.4	ENSP00000294728.2		P19320-1

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80211

AN:

151762

Hom.:

23206

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.502

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.510

Gnomad FIN

AF:

0.682

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.654

Gnomad OTH

AF:

0.517

GnomAD4 exome

AF:

0.603

AC:

38464

AN:

63794

Hom.:

12098

Cov.:

AF XY:

0.599

AC XY:

19681

AN XY:

32860

show subpopulations

African (AFR)

AF:

0.307

AC:

625

AN:

2034

American (AMR)

AF:

0.473

AC:

1177

AN:

2486

Ashkenazi Jewish (ASJ)

AF:

0.543

AC:

1228

AN:

2262

East Asian (EAS)

AF:

0.490

AC:

2113

AN:

4310

South Asian (SAS)

AF:

0.469

AC:

2168

AN:

4620

European-Finnish (FIN)

AF:

0.671

AC:

2057

AN:

3064

Middle Eastern (MID)

AF:

0.565

AC:

182

AN:

322

European-Non Finnish (NFE)

AF:

0.652

AC:

26633

AN:

40850

Other (OTH)

AF:

0.593

AC:

2281

AN:

3846

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

733

1466

2200

2933

3666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.528

AC:

80241

AN:

151880

Hom.:

23218

Cov.:

AF XY:

0.525

AC XY:

39012

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.295

AC:

12221

AN:

41404

American (AMR)

AF:

0.510

AC:

7773

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

1741

AN:

3466

East Asian (EAS)

AF:

0.494

AC:

2553

AN:

5164

South Asian (SAS)

AF:

0.512

AC:

2468

AN:

4822

European-Finnish (FIN)

AF:

0.682

AC:

7201

AN:

10566

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.654

AC:

44401

AN:

67888

Other (OTH)

AF:

0.521

AC:

1100

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1732

3464

5195

6927

8659

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.570

Hom.:

3151

Bravo

AF:

0.505

Asia WGS

AF:

0.522

AC:

1813

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.13

(source)

DANN

Benign

0.63

PhyloP100

-2.1

Mutation Taster

=100/0

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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1-100737839-A-T

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