rs117816525

Variant names:

• chr7-74061120-C-T
• rs117816525
• NM_000501.4:c.1767C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000501.4(ELN):​c.1767C>T​(p.Ala589Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000033 (0 hom.)
• Consequence: ELN NM_000501.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.67
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 7-74061120-C-T is Benign according to our data. Variant chr7-74061120-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 453324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.67 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0000656 (10/152326) while in subpopulation EAS AF = 0.00154 (8/5190). AF 95% confidence interval is 0.000767. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 10 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	NM_000501.4	MANE Select	c.1767C>T	p.Ala589Ala	synonymous	Exon 26 of 33	NP_000492.2
	ELN	NM_001278939.2		c.1953C>T	p.Ala651Ala	synonymous	Exon 27 of 34	NP_001265868.1
	ELN	NM_001278915.2		c.1785C>T	p.Ala595Ala	synonymous	Exon 26 of 33	NP_001265844.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000252034.12	TSL:1 MANE Select	c.1767C>T	p.Ala589Ala	synonymous	Exon 26 of 33	ENSP00000252034.7
	ELN	ENST00000380562.8	TSL:1	c.1785C>T	p.Ala595Ala	synonymous	Exon 26 of 33	ENSP00000369936.4
	ELN	ENST00000458204.5	TSL:1	c.1737C>T	p.Ala579Ala	synonymous	Exon 25 of 32	ENSP00000403162.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000597 AC: 15 AN: 251348 AF XY: 0.0000662

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000707

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000328 AC: 48 AN: 1461796 Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24 AN XY: 727200

African (AFR) AF: 0.0000597 AC: 2 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.000932 AC: 37 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112004

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000656 AC: 10 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41578

American (AMR) AF: 0.00 AC: 0 AN: 15290

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

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68028

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

Alfa AF: 0.0000502 Hom.: 0

Bravo AF: 0.0000756

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Supravalvar aortic stenosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.6
DANN	Benign	0.79
PhyloP100		-3.7

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

Other links and lift over

dbSNP: rs117816525; hg19: chr7-73475450;