1-100730103-G-T

Variant names:

• chr1-100730103-G-T
• rs3917012
• NM_001078.4:c.1204+721G>T

Variant summary

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

The NM_001078.4(VCAM1):​c.1204+721G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,678 control chromosomes in the GnomAD database, including 26,761 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 0.56 (26761 hom., cov: 30)
• Consequence: VCAM1 NM_001078.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.1204+721G>T		intron_variant	Intron 5 of 8	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.1018+721G>T		intron_variant	Intron 5 of 8		NP_001186763.1
VCAM1	NM_080682.3	c.929-1095G>T		intron_variant	Intron 4 of 7		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.1204+721G>T		intron_variant	Intron 5 of 8	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84924 AN: 151560 Hom.: 26752 Cov.: 30

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.773

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.740

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.605

Gnomad NFE AF: 0.705

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.560 AC: 84945 AN: 151678 Hom.: 26761 Cov.: 30 AF XY: 0.559 AC XY: 41465 AN XY: 74124

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.640

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.705

Gnomad4 OTH AF: 0.565

Alfa AF: 0.660 Hom.: 31696

Bravo AF: 0.535

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.89
DANN	Benign	0.60

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: rs3917012; hg19: chr1-101195659;