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: 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: 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.

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.*501_*502insA		3_prime_UTR	Exon 33 of 33	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.*501_*502insA		3_prime_UTR	Exon 34 of 34	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.*501_*502insA		3_prime_UTR	Exon 33 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.*501_*502insA		3_prime_UTR	Exon 33 of 33	ENSP00000252034.7	P15502-2
	ELN	ENST00000458204.5	TSL:1	c.*501_*502insA		3_prime_UTR	Exon 32 of 32	ENSP00000403162.1	E7EN65
	ELN	ENST00000357036.9	TSL:1	c.*501_*502insA		3_prime_UTR	Exon 32 of 32	ENSP00000349540.5	P15502-5

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cutis laxa, autosomal dominant (1)
-	-	1	Supravalvar aortic stenosis (1)

Computational scores

Source: dbNSFP v4.9

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;