1-100721663-A-G

Variant names:

• chr1-100721663-A-G
• rs3176860
• NM_001078.4:c.340+912A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001078.4(VCAM1):​c.340+912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,812 control chromosomes in the GnomAD database, including 15,856 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 0.45 (15856 hom., cov: 32)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.340+912A>G		intron_variant	Intron 2 of 8	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.154+1098A>G		intron_variant	Intron 2 of 8		NP_001186763.1
VCAM1	NM_080682.3	c.340+912A>G		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+912A>G		intron_variant	Intron 2 of 8	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68200 AN: 151694 Hom.: 15842 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.401

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.450 AC: 68260 AN: 151812 Hom.: 15856 Cov.: 32 AF XY: 0.452 AC XY: 33513 AN XY: 74198

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.552

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.460

Alfa AF: 0.410 Hom.: 16881

Bravo AF: 0.466

Asia WGS AF: 0.470 AC: 1630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.23

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: rs3176860; hg19: chr1-101187219;