1-100728649-C-T

Variant names:

• chr1-100728649-C-T
• rs3176867
• NM_001078.4:c.929-458C>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.929-458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 150,442 control chromosomes in the GnomAD database, including 4,015 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 0.21 (4015 hom., cov: 30)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.327 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.929-458C>T		intron	N/A	NP_001069.1
	VCAM1	NM_001199834.2		c.743-458C>T		intron	N/A	NP_001186763.1
	VCAM1	NM_080682.3		c.929-2549C>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.929-458C>T		intron	N/A	ENSP00000294728.2
	VCAM1	ENST00000347652.6	TSL:1	c.929-2549C>T		intron	N/A	ENSP00000304611.2
	VCAM1	ENST00000370119.8	TSL:2	c.743-458C>T		intron	N/A	ENSP00000359137.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31083 AN: 150330 Hom.: 4009 Cov.: 30

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.207 AC: 31082 AN: 150442 Hom.: 4015 Cov.: 30 AF XY: 0.213 AC XY: 15651 AN XY: 73432

African (AFR) AF: 0.0577 AC: 2351 AN: 40764

American (AMR) AF: 0.335 AC: 5058 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1133 AN: 3460

East Asian (EAS) AF: 0.162 AC: 827 AN: 5118

South Asian (SAS) AF: 0.251 AC: 1196 AN: 4760

European-Finnish (FIN) AF: 0.326 AC: 3336 AN: 10248

Middle Eastern (MID) AF: 0.201 AC: 58 AN: 288

European-Non Finnish (NFE) AF: 0.243 AC: 16472 AN: 67700

Other (OTH) AF: 0.244 AC: 511 AN: 2092

Alfa AF: 0.202 Hom.: 2231

Bravo AF: 0.203

Asia WGS AF: 0.189 AC: 656 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.55
PhyloP100		-0.37
Mutation Taster		=99/1	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: rs3176867; hg19: chr1-101194205; COSMIC: COSV54118469;