rs2392221

chr1-100724617-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001078.4(VCAM1):c.662-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,606,466 control chromosomes in the GnomAD database, including 19,404 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.14 (1863 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17541 hom.)
• Consequence: VCAM1 NM_001078.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002185
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 1-100724617-C-T is Benign according to our data. Variant chr1-100724617-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VCAM1	NM_001078.4	c.662-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000294728.7
VCAM1	NM_001199834.2	c.476-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
VCAM1	NM_080682.3	c.662-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VCAM1	ENST00000294728.7	c.662-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001078.4	P1

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21365 AN: 151778 Hom.: 1858 Cov.: 32

Gnomad AFR AF: 0.0758

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.192

GnomAD3 exomes AF: 0.168 AC: 41793 AN: 248244 Hom.: 4167 AF XY: 0.164 AC XY: 22036 AN XY: 134124

Gnomad AFR exome AF: 0.0744

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.141

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.147

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.151 AC: 219070 AN: 1454568 Hom.: 17541 Cov.: 32 AF XY: 0.150 AC XY: 108747 AN XY: 722684

Gnomad4 AFR exome AF: 0.0726

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.148

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.141 AC: 21371 AN: 151898 Hom.: 1863 Cov.: 32 AF XY: 0.142 AC XY: 10536 AN XY: 74218

Gnomad4 AFR AF: 0.0758

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.145

Gnomad4 NFE AF: 0.145

Gnomad4 OTH AF: 0.191

Alfa AF: 0.156 Hom.: 3253

Bravo AF: 0.151

EpiCase AF: 0.151

EpiControl AF: 0.159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	4.4
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0060
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: rs2392221; hg19: chr1-101190173; COSMIC: COSV54119206;