rs200512332

Variant names:

• chr7-74059938-C-A
• rs200512332
• NM_000501.4:c.1467C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-74059938-C-A
• chr7-74059938-C-G
• chr7-74059938-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000501.4(ELN):​c.1467C>A​(p.Val489Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V489V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ELN NM_000501.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 0 publications found

Genes affected

ELN (HGNC:3327): (elastin) This gene encodes a protein that is one of the two components of elastic fibers. Elastic fibers comprise part of the extracellular matrix and confer elasticity to organs and tissues including the heart, skin, lungs, ligaments, and blood vessels. The encoded protein is rich in hydrophobic amino acids such as glycine and proline, which form mobile hydrophobic regions bounded by crosslinks between lysine residues. Degradation products of the encoded protein, known as elastin-derived peptides or elastokines, bind the elastin receptor complex and other receptors and stimulate migration and proliferation of monocytes and skin fibroblasts. Elastokines can also contribute to cancer progression. Deletions and mutations in this gene are associated with supravalvular aortic stenosis (SVAS) and autosomal dominant cutis laxa. [provided by RefSeq, Aug 2017]

ELN-AS1 (HGNC:40212): (ELN antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000501.4. 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
	ELN	NM_000501.4	MANE Select	c.1467C>A	p.Val489Val	synonymous	Exon 23 of 33	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.1554C>A	p.Val518Val	synonymous	Exon 24 of 34	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.1485C>A	p.Val495Val	synonymous	Exon 23 of 33	NP_001265844.1	P15502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000252034.12	TSL:1 MANE Select	c.1467C>A	p.Val489Val	synonymous	Exon 23 of 33	ENSP00000252034.7	P15502-2
	ELN	ENST00000380562.8	TSL:1	c.1485C>A	p.Val495Val	synonymous	Exon 23 of 33	ENSP00000369936.4	P15502-1
	ELN	ENST00000458204.5	TSL:1	c.1437C>A	p.Val479Val	synonymous	Exon 22 of 32	ENSP00000403162.1	E7EN65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.64
DANN	Benign	0.45
PhyloP100		-2.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs200512332; hg19: chr7-73474268;