7-74053320-CTGTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTG

Variant names:

• chr7-74053320-CTGTG-C
• rs10579871
• NM_000501.4:c.1096+47_1096+50delGTGT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000501.4(ELN):​c.1096+47_1096+50delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (21045 hom., cov: 0)
  • Exomes 𝑓: 0.40 (1367 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELN NM_000501.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.33
• Publications: 3 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, Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• supravalvular aortic stenosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• 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 -16 ACMG points.

• BP6: Variant 7-74053320-CTGTG-C is Benign according to our data. Variant chr7-74053320-CTGTG-C is described in ClinVar as Benign. ClinVar VariationId is 402825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 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.1096+47_1096+50delGTGT		intron	N/A	NP_000492.2	P15502-2
	ELN	NM_001278939.2		c.1096+47_1096+50delGTGT		intron	N/A	NP_001265868.1	P15502-3
	ELN	NM_001278915.2		c.1096+47_1096+50delGTGT		intron	N/A	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.1096+12_1096+15delTGTG		intron	N/A	ENSP00000252034.7	P15502-2
	ELN	ENST00000380562.8	TSL:1	c.1096+12_1096+15delTGTG		intron	N/A	ENSP00000369936.4	P15502-1
	ELN	ENST00000458204.5	TSL:1	c.1066+12_1066+15delTGTG		intron	N/A	ENSP00000403162.1	E7EN65

Frequencies

GnomAD3 genomes AF: 0.546 AC: 78542 AN: 143916 Hom.: 21037 Cov.: 0

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.572

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.561

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.398 AC: 563021 AN: 1414038 Hom.: 1367 AF XY: 0.397 AC XY: 278243 AN XY: 700706

African (AFR) AF: 0.364 AC: 11706 AN: 32190

American (AMR) AF: 0.395 AC: 15515 AN: 39318

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 10457 AN: 25202

East Asian (EAS) AF: 0.403 AC: 15123 AN: 37496

South Asian (SAS) AF: 0.387 AC: 31896 AN: 82338

European-Finnish (FIN) AF: 0.410 AC: 20041 AN: 48844

Middle Eastern (MID) AF: 0.392 AC: 1649 AN: 4212

European-Non Finnish (NFE) AF: 0.399 AC: 433390 AN: 1086188

Other (OTH) AF: 0.399 AC: 23244 AN: 58250

GnomAD4 genome AF: 0.546 AC: 78583 AN: 144018 Hom.: 21045 Cov.: 0 AF XY: 0.547 AC XY: 38210 AN XY: 69822

African (AFR) AF: 0.486 AC: 18824 AN: 38704

American (AMR) AF: 0.601 AC: 8650 AN: 14400

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2059 AN: 3392

East Asian (EAS) AF: 0.572 AC: 2792 AN: 4878

South Asian (SAS) AF: 0.541 AC: 2353 AN: 4352

European-Finnish (FIN) AF: 0.576 AC: 5419 AN: 9416

Middle Eastern (MID) AF: 0.560 AC: 158 AN: 282

European-Non Finnish (NFE) AF: 0.559 AC: 36756 AN: 65712

Other (OTH) AF: 0.563 AC: 1123 AN: 1994

Alfa AF: 0.437 Hom.: 744

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Supravalvar aortic stenosis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
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: rs10579871; hg19: chr7-73467650;