rs3176877

Variant names:

• chr1-100737839-A-C
• rs3176877
• NM_001078.4:c.2060-284A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-100737839-A-C
• chr1-100737839-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001078.4(VCAM1):​c.2060-284A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 9 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAM1	NM_001078.4	MANE Select	c.2060-284A>C		intron	N/A	NP_001069.1	P19320-1
	VCAM1	NM_001199834.2		c.1874-284A>C		intron	N/A	NP_001186763.1	P19320-3
	VCAM1	NM_080682.3		c.1784-284A>C		intron	N/A	NP_542413.1	P19320-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VCAM1	ENST00000294728.7	TSL:1 MANE Select	c.2060-284A>C		intron	N/A	ENSP00000294728.2	P19320-1
	VCAM1	ENST00000347652.6	TSL:1	c.1784-284A>C		intron	N/A	ENSP00000304611.2	P19320-2
	VCAM1	ENST00000855907.1		c.1964-284A>C		intron	N/A	ENSP00000525966.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 64074 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 33022

African (AFR) AF: 0.00 AC: 0 AN: 2038

American (AMR) AF: 0.00 AC: 0 AN: 2498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2278

East Asian (EAS) AF: 0.00 AC: 0 AN: 4332

South Asian (SAS) AF: 0.00 AC: 0 AN: 4640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3076

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 322

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 41020

Other (OTH) AF: 0.00 AC: 0 AN: 3870

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 3151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.64
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism

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: rs3176877; hg19: chr1-101203395;