dbSNP rs748417631: VCAM1:p.Ala168Thr (chr1-100723181-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001078.4(VCAM1):c.502G>A(p.Ala168Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

VCAM1
NM_001078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0540

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018824935).

BS2

High AC in GnomAdExome4 at 20 AD gene.

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.502G>A	p.Ala168Thr	missense	Exon 3 of 9	NP_001069.1	P19320-1
VCAM1	NM_001199834.2		c.316G>A	p.Ala106Thr	missense	Exon 3 of 9	NP_001186763.1	P19320-3
VCAM1	NM_080682.3		c.502G>A	p.Ala168Thr	missense	Exon 3 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.502G>A	p.Ala168Thr	missense	Exon 3 of 9	ENSP00000294728.2	P19320-1
VCAM1	ENST00000347652.6	TSL:1	c.502G>A	p.Ala168Thr	missense	Exon 3 of 8	ENSP00000304611.2	P19320-2
VCAM1	ENST00000855907.1		c.502G>A	p.Ala168Thr	missense	Exon 3 of 9	ENSP00000525966.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000798

AC:

AN:

250574

AF XY:

0.0000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000465

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1460984

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726794

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.000449

AC:

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111486

Other (OTH)

AF:

0.00

AC:

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000132

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41432

American (AMR)

AF:

0.000131

AC:

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67980

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.56

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.093

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.042

M_CAP

Benign

0.0035

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PhyloP100

0.054

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.34

REVEL

Benign

0.0060

Sift

Benign

0.85

Sift4G

Benign

0.68

Polyphen

0.0010

Vest4

0.055

MutPred

0.37

Gain of phosphorylation at A168 (P = 0.0226)

MVP

0.23

MPC

0.15

ClinPred

0.014

GERP RS

-3.4

Varity_R

0.11

gMVP

0.34

Mutation Taster

=92/8

polymorphism

(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