dbSNP rs3176877: 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. Variant has been reported in ClinVar as (no stars).

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:

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 (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.649 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	Effect	Exon Rank	Protein	UniProt
VCAM1	NM_001078.4	MANE Select	c.2060-284A>T	intron	N/A	NP_001069.1	P19320-1
VCAM1	NM_001199834.2		c.1874-284A>T	intron	N/A	NP_001186763.1	P19320-3
VCAM1	NM_080682.3		c.1784-284A>T	intron	N/A	NP_542413.1	P19320-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
VCAM1	ENST00000294728.7	TSL:1 MANE Select	c.2060-284A>T	intron	N/A	ENSP00000294728.2	P19320-1
VCAM1	ENST00000347652.6	TSL:1	c.1784-284A>T	intron	N/A	ENSP00000304611.2	P19320-2
VCAM1	ENST00000855907.1		c.1964-284A>T	intron	N/A	ENSP00000525966.1

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

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<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:

0.528

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

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.570

Hom.:

3151

Bravo

AF:

0.505

Asia WGS

AF:

0.522

AC:

1813

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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

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