NM_000501.4:c.1434C>T

Variant names:

• chr7-74059905-C-T
• rs781926084
• NM_000501.4:c.1434C>T

Variant summary

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

The NM_000501.4(ELN):​c.1434C>T​(p.Gly478Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000937 in 1,280,734 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: 32)
  • Exomes 𝑓: 0.0000094 (0 hom.)
• Consequence: ELN NM_000501.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.39
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 7-74059905-C-T is Benign according to our data. Variant chr7-74059905-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1035322.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.39 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 12 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	NM_000501.4	MANE Select	c.1434C>T	p.Gly478Gly	synonymous	Exon 23 of 33	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.1521C>T	p.Gly507Gly	synonymous	Exon 24 of 34	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.1452C>T	p.Gly484Gly	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.1434C>T	p.Gly478Gly	synonymous	Exon 23 of 33	ENSP00000252034.7	P15502-2
	ELN	ENST00000380562.8	TSL:1	c.1452C>T	p.Gly484Gly	synonymous	Exon 23 of 33	ENSP00000369936.4	P15502-1
	ELN	ENST00000458204.5	TSL:1	c.1404C>T	p.Gly468Gly	synonymous	Exon 22 of 32	ENSP00000403162.1	E7EN65

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251468 AF XY: 0.0000147

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000937 AC: 12 AN: 1280734 Hom.: 0 Cov.: 20 AF XY: 0.0000108 AC XY: 7 AN XY: 646402

African (AFR) AF: 0.0000334 AC: 1 AN: 29918

American (AMR) AF: 0.00 AC: 0 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24978

East Asian (EAS) AF: 0.00 AC: 0 AN: 38836

South Asian (SAS) AF: 0.0000483 AC: 4 AN: 82746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5436

European-Non Finnish (NFE) AF: 0.00000634 AC: 6 AN: 946720

Other (OTH) AF: 0.00 AC: 0 AN: 54246

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Supravalvar aortic stenosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.59
DANN	Benign	0.77
PhyloP100		-3.4

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: rs781926084; hg19: chr7-73474235;