1-100720528-T-C

Variant names:

• chr1-100720528-T-C
• rs145509462
• NM_001078.4:c.117T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001078.4(VCAM1):​c.117T>C​(p.Ile39Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,340 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (5 hom.)
• Consequence: VCAM1 NM_001078.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.688

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-100720528-T-C is Benign according to our data. Variant chr1-100720528-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 713843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.688 with no splicing effect.
• BS2: High AC in GnomAd4 at 129 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VCAM1	NM_001078.4	c.117T>C	p.Ile39Ile	synonymous_variant	Exon 2 of 9	ENST00000294728.7	NP_001069.1
VCAM1	NM_001199834.2	c.117T>C	p.Ile39Ile	synonymous_variant	Exon 2 of 9		NP_001186763.1
VCAM1	NM_080682.3	c.117T>C	p.Ile39Ile	synonymous_variant	Exon 2 of 8		NP_542413.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VCAM1	ENST00000294728.7	c.117T>C	p.Ile39Ile	synonymous_variant	Exon 2 of 9	1	NM_001078.4	ENSP00000294728.2

Frequencies

GnomAD3 genomes AF: 0.000848 AC: 129 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000938 AC: 235 AN: 250472 AF XY: 0.000828

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00120

Gnomad NFE exome AF: 0.00166

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00180 AC: 2633 AN: 1461076 Hom.: 5 Cov.: 31 AF XY: 0.00175 AC XY: 1269 AN XY: 726832

African (AFR) AF: 0.000389 AC: 13 AN: 33414

American (AMR) AF: 0.000179 AC: 8 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86224

European-Finnish (FIN) AF: 0.00159 AC: 85 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00222 AC: 2470 AN: 1111460

Other (OTH) AF: 0.000911 AC: 55 AN: 60346

GnomAD4 genome AF: 0.000847 AC: 129 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000752 AC XY: 56 AN XY: 74442

African (AFR) AF: 0.000313 AC: 13 AN: 41568

American (AMR) AF: 0.000327 AC: 5 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00150 AC: 102 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.000672

EpiCase AF: 0.00164

EpiControl AF: 0.00166

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	9.2
DANN	Benign	0.74
PhyloP100		0.69
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Other links and lift over

dbSNP: rs145509462; hg19: chr1-101186084;