ENST00000380562:c.-37G>C

Variant names:

• chr7-74028151-G-C
• rs782267385
• ENST00000380562.8:c.-37G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000380562.8(ELN):​c.-37G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000231 in 1,297,986 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: ELN ENST00000380562.8 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.11
• 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, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-74028151-G-C is Benign according to our data. Variant chr7-74028151-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 508478.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380562.8. 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.-37G>C		upstream_gene	N/A	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.-37G>C		upstream_gene	N/A	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.-37G>C		upstream_gene	N/A	NP_001265844.1	P15502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000380562.8	TSL:1	c.-37G>C		5_prime_UTR	Exon 1 of 33	ENSP00000369936.4	P15502-1
	ELN	ENST00000869821.1		c.-37G>C		5_prime_UTR	Exon 1 of 33	ENSP00000539880.1
	ELN	ENST00000869840.1		c.-37G>C		5_prime_UTR	Exon 1 of 33	ENSP00000539899.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000231 AC: 3 AN: 1297986 Hom.: 0 Cov.: 32 AF XY: 0.00000311 AC XY: 2 AN XY: 642800

African (AFR) AF: 0.00 AC: 0 AN: 28928

American (AMR) AF: 0.00 AC: 0 AN: 39444

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20526

East Asian (EAS) AF: 0.00 AC: 0 AN: 26934

South Asian (SAS) AF: 0.00 AC: 0 AN: 83782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4912

European-Non Finnish (NFE) AF: 0.00000298 AC: 3 AN: 1006098

Other (OTH) AF: 0.00 AC: 0 AN: 49874

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.90
PhyloP100		3.1
PromoterAI		-0.27	Neutral

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: rs782267385; hg19: chr7-73442481;