dbSNP rs3176878: VCAM1:p.Asp693Asp (chr1-100738142-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001078.4(VCAM1):c.2079C>T(p.Asp693Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,612,012 control chromosomes in the GnomAD database, including 21,597 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.16 ( 2154 hom., cov: 32)

Exomes 𝑓: 0.16 ( 19443 hom. )

Consequence

VCAM1
NM_001078.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.196

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 1-100738142-C-T is Benign according to our data. Variant chr1-100738142-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.196 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4 link	c.2079C>T	p.Asp693Asp	synonymous_variant	Exon 9 of 9	ENST00000294728.7	NP_001069.1	P19320-1
VCAM1	NM_001199834.2 link	c.1893C>T	p.Asp631Asp	synonymous_variant	Exon 9 of 9		NP_001186763.1	P19320-3
VCAM1	NM_080682.3 link	c.1803C>T	p.Asp601Asp	synonymous_variant	Exon 8 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.2079C>T	p.Asp693Asp	synonymous_variant	Exon 9 of 9	1	NM_001078.4	ENSP00000294728.2		P19320-1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

24478

AN:

151994

Hom.:

2153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.0133

Gnomad SAS

AF:

0.0870

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.165

Gnomad OTH

AF:

0.176

GnomAD2 exomes

AF:

0.162

AC:

40559

AN:

250800

AF XY:

0.156

show subpopulations

Gnomad AFR exome

AF:

0.160

Gnomad AMR exome

AF:

0.275

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.127

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.175

GnomAD4 exome

AF:

0.158

AC:

230393

AN:

1459900

Hom.:

19443

Cov.:

AF XY:

0.156

AC XY:

113170

AN XY:

726242

show subpopulations

Gnomad4 AFR exome

AF:

0.156

AC:

5216

AN:

33426

Gnomad4 AMR exome

AF:

0.266

AC:

11897

AN:

44642

Gnomad4 ASJ exome

AF:

0.264

AC:

6875

AN:

26078

Gnomad4 EAS exome

AF:

0.00767

AC:

304

AN:

39630

Gnomad4 SAS exome

AF:

0.0931

AC:

8008

AN:

86056

Gnomad4 FIN exome

AF:

0.136

AC:

7251

AN:

53388

Gnomad4 NFE exome

AF:

0.163

AC:

180598

AN:

1110698

Gnomad4 Remaining exome

AF:

0.157

AC:

9495

AN:

60316

Heterozygous variant carriers

9465

18930

28396

37861

47326

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

6362

12724

19086

25448

31810

<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:

0.161

AC:

24484

AN:

152112

Hom.:

2154

Cov.:

AF XY:

0.157

AC XY:

11678

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.157

AC:

0.15708

AN:

0.15708

Gnomad4 AMR

AF:

0.232

AC:

0.232299

AN:

0.232299

Gnomad4 ASJ

AF:

0.281

AC:

0.281051

AN:

0.281051

Gnomad4 EAS

AF:

0.0129

AC:

0.0129294

AN:

0.0129294

Gnomad4 SAS

AF:

0.0872

AC:

0.0872358

AN:

0.0872358

Gnomad4 FIN

AF:

0.113

AC:

0.112623

AN:

0.112623

Gnomad4 NFE

AF:

0.165

AC:

0.164557

AN:

0.164557

Gnomad4 OTH

AF:

0.174

AC:

0.173913

AN:

0.173913

Heterozygous variant carriers

1043

2085

3128

4170

5213

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

258

516

774

1032

1290

<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:

0.168

Hom.:

4748

Bravo

AF:

0.169

Asia WGS

AF:

0.0610

AC:

212

AN:

3478

EpiCase

AF:

0.166

EpiControl

AF:

0.162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.2

DANN

Benign

0.30

Mutation Taster

=100/0

polymorphism (auto)

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