1-100724617-C-T

Variant names:

• chr1-100724617-C-T
• rs2392221
• NM_001078.4:c.662-7C>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.662-7C>T variant causes a splice region, 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1863 hom., cov: 32)
  • Exomes 𝑓: 0.15 (17541 hom.)
• Consequence: VCAM1 NM_001078.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002185
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 28 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=-0.67).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

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.662-7C>T		splice_region intron	N/A	NP_001069.1	P19320-1
	VCAM1	NM_001199834.2		c.476-7C>T		splice_region intron	N/A	NP_001186763.1	P19320-3
	VCAM1	NM_080682.3		c.662-7C>T		splice_region 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.662-7C>T		splice_region intron	N/A	ENSP00000294728.2	P19320-1
	VCAM1	ENST00000347652.6	TSL:1	c.662-7C>T		splice_region intron	N/A	ENSP00000304611.2	P19320-2
	VCAM1	ENST00000855907.1		c.662-7C>T		splice_region intron	N/A	ENSP00000525966.1

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

GnomAD2 exomes AF: 0.168 AC: 41793 AN: 248244 AF XY: 0.164

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 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

African (AFR) AF: 0.0726 AC: 2398 AN: 33052

American (AMR) AF: 0.300 AC: 13187 AN: 43972

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 7372 AN: 25914

East Asian (EAS) AF: 0.148 AC: 5848 AN: 39550

South Asian (SAS) AF: 0.139 AC: 11877 AN: 85582

European-Finnish (FIN) AF: 0.140 AC: 7485 AN: 53294

Middle Eastern (MID) AF: 0.187 AC: 1073 AN: 5730

European-Non Finnish (NFE) AF: 0.145 AC: 160432 AN: 1107430

Other (OTH) AF: 0.157 AC: 9398 AN: 60044

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

African (AFR) AF: 0.0758 AC: 3141 AN: 41462

American (AMR) AF: 0.255 AC: 3890 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 976 AN: 3472

East Asian (EAS) AF: 0.143 AC: 736 AN: 5152

South Asian (SAS) AF: 0.137 AC: 658 AN: 4806

European-Finnish (FIN) AF: 0.145 AC: 1528 AN: 10570

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.145 AC: 9838 AN: 67894

Other (OTH) AF: 0.191 AC: 401 AN: 2104

Alfa AF: 0.155 Hom.: 4236

Bravo AF: 0.151

EpiCase AF: 0.151

EpiControl AF: 0.159

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.4
DANN	Benign	0.44
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2392221; hg19: chr1-101190173; COSMIC: COSV54119206;