rs34208922

Variant names:

• chr7-74069201-C-CA
• rs34208922
• NM_000501.4:c.*501_*502insA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000501.4(ELN):​c.*501_*502insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7978 hom., cov: 0)
  • Exomes 𝑓: 0.23 (3171 hom.)
• Consequence: ELN NM_000501.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.669
• Publications: 9 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: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, Genomics England PanelApp, G2P
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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 -10 ACMG points.

• BP6: Variant 7-74069201-C-CA is Benign according to our data. Variant chr7-74069201-C-CA is described in ClinVar as Benign. ClinVar VariationId is 360671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4	c.*501_*502insA		3_prime_UTR_variant	Exon 33 of 33	ENST00000252034.12	NP_000492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12	c.*501_*502insA		3_prime_UTR_variant	Exon 33 of 33	1	NM_000501.4	ENSP00000252034.7

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45070 AN: 151896 Hom.: 7938 Cov.: 0

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.0800

Gnomad SAS AF: 0.256

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.282

GnomAD4 exome AF: 0.229 AC: 24243 AN: 105850 Hom.: 3171 Cov.: 0 AF XY: 0.228 AC XY: 11510 AN XY: 50420

African (AFR) AF: 0.485 AC: 2199 AN: 4538

American (AMR) AF: 0.206 AC: 1104 AN: 5350

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 1001 AN: 5488

East Asian (EAS) AF: 0.101 AC: 1287 AN: 12798

South Asian (SAS) AF: 0.243 AC: 964 AN: 3966

European-Finnish (FIN) AF: 0.139 AC: 163 AN: 1174

Middle Eastern (MID) AF: 0.268 AC: 150 AN: 560

European-Non Finnish (NFE) AF: 0.240 AC: 15367 AN: 64010

Other (OTH) AF: 0.252 AC: 2008 AN: 7966

GnomAD4 genome AF: 0.297 AC: 45157 AN: 152014 Hom.: 7978 Cov.: 0 AF XY: 0.290 AC XY: 21550 AN XY: 74316

African (AFR) AF: 0.492 AC: 20393 AN: 41414

American (AMR) AF: 0.232 AC: 3539 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 645 AN: 3472

East Asian (EAS) AF: 0.0799 AC: 413 AN: 5166

South Asian (SAS) AF: 0.257 AC: 1236 AN: 4816

European-Finnish (FIN) AF: 0.151 AC: 1603 AN: 10600

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16420 AN: 67964

Other (OTH) AF: 0.278 AC: 586 AN: 2106

Alfa AF: 0.270 Hom.: 757

Bravo AF: 0.307

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cutis laxa, autosomal dominant Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Supravalvar aortic stenosis Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.67
Mutation Taster		=100/0	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: rs34208922; hg19: chr7-73483531; COSMIC: COSV52706606; COSMIC: COSV52706606;