NM_000501.4:c.1415-722T>C

Variant names:

• chr7-74059164-T-C
• rs2528795
• NM_000501.4:c.1415-722T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000501.4(ELN):​c.1415-722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,932 control chromosomes in the GnomAD database, including 6,227 homozygotes. 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 0.26 (6227 hom., cov: 32)
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

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.1415-722T>C		intron	N/A	NP_000492.2
	ELN	NM_001278939.2		c.1502-722T>C		intron	N/A	NP_001265868.1
	ELN	NM_001278915.2		c.1415-704T>C		intron	N/A	NP_001265844.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELN	ENST00000252034.12	TSL:1 MANE Select	c.1415-722T>C		intron	N/A	ENSP00000252034.7
	ELN	ENST00000380562.8	TSL:1	c.1415-704T>C		intron	N/A	ENSP00000369936.4
	ELN	ENST00000458204.5	TSL:1	c.1385-722T>C		intron	N/A	ENSP00000403162.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40156 AN: 151814 Hom.: 6192 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.237

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40243 AN: 151932 Hom.: 6227 Cov.: 32 AF XY: 0.260 AC XY: 19293 AN XY: 74252

African (AFR) AF: 0.422 AC: 17451 AN: 41334

American (AMR) AF: 0.189 AC: 2887 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 630 AN: 3472

East Asian (EAS) AF: 0.0683 AC: 354 AN: 5180

South Asian (SAS) AF: 0.171 AC: 824 AN: 4810

European-Finnish (FIN) AF: 0.201 AC: 2119 AN: 10562

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15274 AN: 67980

Other (OTH) AF: 0.234 AC: 494 AN: 2110

Alfa AF: 0.235 Hom.: 5961

Bravo AF: 0.268

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.24
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs2528795; hg19: chr7-73473494;