rs3783611

chr1-100729131-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001078.4(VCAM1):c.953C>T(p.Ser318Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,602,138 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.0063 (11 hom., cov: 31)
  • Exomes 𝑓: 0.00062 (12 hom.)
• Consequence: VCAM1 NM_001078.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.589

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048876703).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00632 (962/152178) while in subpopulation AFR AF= 0.0222 (923/41526). AF 95% confidence interval is 0.021. There are 11 homozygotes in gnomad4. There are 448 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 953 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAM1	NM_001078.4	c.953C>T	p.Ser318Phe	missense_variant	5/9	ENST00000294728.7
VCAM1	NM_001199834.2	c.767C>T	p.Ser256Phe	missense_variant	5/9
VCAM1	NM_080682.3	c.929-2067C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7	c.953C>T	p.Ser318Phe	missense_variant	5/9	1	NM_001078.4	P1

Frequencies

GnomAD3 genomes AF: 0.00627 AC: 953 AN: 152060 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00197

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: 0.0000147

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00162 AC: 396 AN: 244150 Hom.: 7 AF XY: 0.00116 AC XY: 153 AN XY: 131752

Gnomad AFR exome AF: 0.0222

Gnomad AMR exome AF: 0.000978

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000272

Gnomad OTH exome AF: 0.000337

GnomAD4 exome AF: 0.000618 AC: 896 AN: 1449960 Hom.: 12 Cov.: 30 AF XY: 0.000536 AC XY: 386 AN XY: 719976

Gnomad4 AFR exome AF: 0.0215

Gnomad4 AMR exome AF: 0.00100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000829

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000118

Gnomad4 OTH exome AF: 0.00189

GnomAD4 genome AF: 0.00632 AC: 962 AN: 152178 Hom.: 11 Cov.: 31 AF XY: 0.00602 AC XY: 448 AN XY: 74388

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00139 Hom.: 3

Bravo AF: 0.00728

ESP6500AA AF: 0.0236 AC: 104

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00194 AC: 235

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	15
Dann	Uncertain	0.99
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.66	T;T
MetaRNN	Benign	0.0049	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Benign	0.075
Sift	Benign	0.064	T;T
Sift4G	Uncertain	0.0070	D;D
Polyphen		0.49	.;P
Vest4		0.17
MVP		0.21
MPC		0.23
ClinPred		0.059	T
GERP RS		-1.3
Varity_R		0.082
gMVP		0.45

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

Other links and lift over

dbSNP: rs3783611; hg19: chr1-101194687; COSMIC: COSV54122984;