rs537200597

Variant names:

• chr7-74028118-G-A
• rs537200597
• ENST00000869840.1:c.-70G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-74028118-G-A
• chr7-74028118-G-C
• chr7-74028118-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000445912.5(ELN):​c.-70G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00096 in 569,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00033 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: ELN ENST00000445912.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.927
• 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 Gene-Disease associations (from GenCC):

• cutis laxa, autosomal dominant 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• autosomal dominant cutis laxa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000333 (39/117042) while in subpopulation NFE AF = 0.000554 (33/59528). AF 95% confidence interval is 0.000405. There are 0 homozygotes in GnomAd4. There are 18 alleles in the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High AC in GnomAd4 at 39 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000445912.5. 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.-70G>A		upstream_gene	N/A	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.-70G>A		upstream_gene	N/A	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.-70G>A		upstream_gene	N/A	NP_001265844.1	P15502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000869840.1		c.-70G>A		5_prime_UTR	Exon 1 of 33	ENSP00000539899.1
	ELN	ENST00000869804.1		c.-70G>A		5_prime_UTR	Exon 1 of 33	ENSP00000539863.1
	ELN	ENST00000869842.1		c.-70G>A		5_prime_UTR	Exon 1 of 33	ENSP00000539901.1

Frequencies

GnomAD3 genomes AF: 0.000333 AC: 39 AN: 117042 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000554

Gnomad OTH AF: 0.00129

GnomAD4 exome AF: 0.00112 AC: 508 AN: 452546 Hom.: 0 Cov.: 15 AF XY: 0.00101 AC XY: 236 AN XY: 232842

African (AFR) AF: 0.000507 AC: 6 AN: 11824

American (AMR) AF: 0.0000754 AC: 2 AN: 26528

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10158

East Asian (EAS) AF: 0.00 AC: 0 AN: 9510

South Asian (SAS) AF: 0.0000199 AC: 1 AN: 50334

European-Finnish (FIN) AF: 0.0000492 AC: 1 AN: 20344

Middle Eastern (MID) AF: 0.000371 AC: 1 AN: 2692

European-Non Finnish (NFE) AF: 0.00159 AC: 484 AN: 304136

Other (OTH) AF: 0.000764 AC: 13 AN: 17020

GnomAD4 genome AF: 0.000333 AC: 39 AN: 117042 Hom.: 0 Cov.: 29 AF XY: 0.000332 AC XY: 18 AN XY: 54266

African (AFR) AF: 0.000130 AC: 4 AN: 30794

American (AMR) AF: 0.00 AC: 0 AN: 9504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3148

East Asian (EAS) AF: 0.00 AC: 0 AN: 3378

South Asian (SAS) AF: 0.00 AC: 0 AN: 3172

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 196

European-Non Finnish (NFE) AF: 0.000554 AC: 33 AN: 59528

Other (OTH) AF: 0.00129 AC: 2 AN: 1552

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000283

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.92
PhyloP100		0.93
PromoterAI		0.014	Neutral
Mutation Taster		=299/1	polymorphism

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: rs537200597; hg19: chr7-73442448;