7-74053320-CTGTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTG

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_000501.4(ELN):c.1096+49_1096+50delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,549,400 control chromosomes in the GnomAD database, including 228 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.047 ( 221 hom., cov: 0)

Exomes 𝑓: 0.051 ( 7 hom. )

Consequence

ELN
NM_000501.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 0.780

Publications

3 publications found

Variant links:

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

ELN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant 7-74053320-CTG-C is Benign according to our data. Variant chr7-74053320-CTG-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 360646.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4 link	c.1096+49_1096+50delGT		intron_variant	Intron 18 of 32	ENST00000252034.12	NP_000492.2	P15502-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELN	ENST00000252034.12 link	c.1096+12_1096+13delTG		intron_variant	Intron 18 of 32	1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.0472

AC:

6789

AN:

143986

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0881

Gnomad AMI

AF:

0.0180

Gnomad AMR

AF:

0.0412

Gnomad ASJ

AF:

0.0304

Gnomad EAS

AF:

0.0553

Gnomad SAS

AF:

0.0509

Gnomad FIN

AF:

0.0424

Gnomad MID

AF:

0.0263

Gnomad NFE

AF:

0.0256

Gnomad OTH

AF:

0.0457

GnomAD4 exome

AF:

0.0510

AC:

71727

AN:

1405312

Hom.:

AF XY:

0.0513

AC XY:

35702

AN XY:

696486

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.101

AC:

3235

AN:

32074

American (AMR)

AF:

0.0498

AC:

1957

AN:

39310

Ashkenazi Jewish (ASJ)

AF:

0.0423

AC:

1066

AN:

25174

East Asian (EAS)

AF:

0.0930

AC:

3463

AN:

37246

South Asian (SAS)

AF:

0.0644

AC:

5280

AN:

81984

European-Finnish (FIN)

AF:

0.0625

AC:

3037

AN:

48626

Middle Eastern (MID)

AF:

0.0521

AC:

219

AN:

4204

European-Non Finnish (NFE)

AF:

0.0466

AC:

50247

AN:

1078716

Other (OTH)

AF:

0.0556

AC:

3223

AN:

57978

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.328

Heterozygous variant carriers

4289

8577

12866

17154

21443

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1990

3980

5970

7960

9950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0472

AC:

6805

AN:

144088

Hom.:

221

Cov.:

AF XY:

0.0485

AC XY:

3390

AN XY:

69870

show subpopulations

African (AFR)

AF:

0.0883

AC:

3420

AN:

38718

American (AMR)

AF:

0.0411

AC:

592

AN:

14408

Ashkenazi Jewish (ASJ)

AF:

0.0304

AC:

103

AN:

3390

East Asian (EAS)

AF:

0.0554

AC:

271

AN:

4890

South Asian (SAS)

AF:

0.0503

AC:

220

AN:

4370

European-Finnish (FIN)

AF:

0.0424

AC:

398

AN:

9396

Middle Eastern (MID)

AF:

0.0248

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.0256

AC:

1685

AN:

65754

Other (OTH)

AF:

0.0467

AC:

AN:

1992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

287

574

860

1147

1434

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0397

Hom.:

744

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Supravalvar aortic stenosis

Uncertain:1Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cutis laxa, autosomal dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Aug 18, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over