NM_001078.4:c.340+1014C>T

Variant names:

• chr1-100721765-C-T
• rs3176861
• NM_001078.4:c.340+1014C>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.340+1014C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 151,996 control chromosomes in the GnomAD database, including 3,038 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 0.18 (3038 hom., cov: 32)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 20 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.340+1014C>T		intron_variant	Intron 2 of 8	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.154+1200C>T		intron_variant	Intron 2 of 8		NP_001186763.1
VCAM1	NM_080682.3	c.340+1014C>T		intron_variant	Intron 2 of 7		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.340+1014C>T		intron_variant	Intron 2 of 8	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes AF: 0.179 AC: 27197 AN: 151878 Hom.: 3037 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.179 AC: 27199 AN: 151996 Hom.: 3038 Cov.: 32 AF XY: 0.183 AC XY: 13628 AN XY: 74294

African (AFR) AF: 0.0461 AC: 1912 AN: 41518

American (AMR) AF: 0.233 AC: 3546 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3468

East Asian (EAS) AF: 0.257 AC: 1321 AN: 5144

South Asian (SAS) AF: 0.357 AC: 1717 AN: 4810

European-Finnish (FIN) AF: 0.216 AC: 2285 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15201 AN: 67932

Other (OTH) AF: 0.167 AC: 353 AN: 2114

Alfa AF: 0.220 Hom.: 2322

Bravo AF: 0.170

Asia WGS AF: 0.302 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.46
PhyloP100		-0.24
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: rs3176861; hg19: chr1-101187321;