chr1-100733152-C-T

Variant names:

• chr1-100733152-C-T
• rs3181088
• NM_001078.4:c.1792+468C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001078.4(VCAM1):​c.1792+468C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,220 control chromosomes in the GnomAD database, including 1,710 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 0.13 (1710 hom., cov: 32)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 24 publications found

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]

ENSG00000299357 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.18 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAM1	NM_001078.4	MANE Select	c.1792+468C>T		intron	N/A	NP_001069.1
	VCAM1	NM_001199834.2		c.1606+468C>T		intron	N/A	NP_001186763.1
	VCAM1	NM_080682.3		c.1516+468C>T		intron	N/A	NP_542413.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAM1	ENST00000294728.7	TSL:1 MANE Select	c.1792+468C>T		intron	N/A	ENSP00000294728.2
	VCAM1	ENST00000347652.6	TSL:1	c.1516+468C>T		intron	N/A	ENSP00000304611.2
	VCAM1	ENST00000370119.8	TSL:2	c.1606+468C>T		intron	N/A	ENSP00000359137.3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19623 AN: 152102 Hom.: 1709 Cov.: 32

Gnomad AFR AF: 0.0327

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.0937

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19622 AN: 152220 Hom.: 1710 Cov.: 32 AF XY: 0.128 AC XY: 9538 AN XY: 74418

African (AFR) AF: 0.0326 AC: 1356 AN: 41546

American (AMR) AF: 0.0921 AC: 1408 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 325 AN: 3470

East Asian (EAS) AF: 0.120 AC: 622 AN: 5174

South Asian (SAS) AF: 0.148 AC: 712 AN: 4822

European-Finnish (FIN) AF: 0.215 AC: 2282 AN: 10594

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12455 AN: 68002

Other (OTH) AF: 0.118 AC: 249 AN: 2116

Alfa AF: 0.160 Hom.: 4322

Bravo AF: 0.116

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.49
PhyloP100		0.23
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

Other links and lift over

dbSNP: rs3181088; hg19: chr1-101198708;