NM_000501.4:c.2087-34C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000501.4(ELN):c.2087-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,613,298 control chromosomes in the GnomAD database, including 12,147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.12 ( 1039 hom., cov: 31)

Exomes 𝑓: 0.12 ( 11108 hom. )

Consequence

ELN
NM_000501.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.687

Publications

17 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 -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-74066698-C-T is Benign according to our data. Variant chr7-74066698-C-T is described in ClinVar as Benign. ClinVar VariationId is 1236531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4 link	c.2087-34C>T		intron_variant	Intron 31 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.2087-34C>T		intron_variant	Intron 31 of 32	1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17548

AN:

152118

Hom.:

1040

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.0911

Gnomad ASJ

AF:

0.0760

Gnomad EAS

AF:

0.0526

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.0985

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.105

AC:

26438

AN:

251286

AF XY:

0.105

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.0820

Gnomad ASJ exome

AF:

0.0826

Gnomad EAS exome

AF:

0.0492

Gnomad FIN exome

AF:

0.0913

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.108

GnomAD4 exome

AF:

0.120

AC:

175147

AN:

1461064

Hom.:

11108

Cov.:

AF XY:

0.119

AC XY:

86352

AN XY:

726818

show subpopulations

African (AFR)

AF:

0.133

AC:

4459

AN:

33454

American (AMR)

AF:

0.0815

AC:

3642

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0840

AC:

2195

AN:

26116

East Asian (EAS)

AF:

0.0446

AC:

1768

AN:

39682

South Asian (SAS)

AF:

0.0926

AC:

7984

AN:

86234

European-Finnish (FIN)

AF:

0.0933

AC:

4981

AN:

53368

Middle Eastern (MID)

AF:

0.0631

AC:

364

AN:

5768

European-Non Finnish (NFE)

AF:

0.129

AC:

143310

AN:

1111388

Other (OTH)

AF:

0.107

AC:

6444

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

8459

16919

25378

33838

42297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5180

10360

15540

20720

25900

<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:

0.115

AC:

17554

AN:

152234

Hom.:

1039

Cov.:

AF XY:

0.114

AC XY:

8504

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.131

AC:

5436

AN:

41534

American (AMR)

AF:

0.0910

AC:

1391

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0760

AC:

264

AN:

3472

East Asian (EAS)

AF:

0.0527

AC:

273

AN:

5180

South Asian (SAS)

AF:

0.0889

AC:

429

AN:

4828

European-Finnish (FIN)

AF:

0.0985

AC:

1046

AN:

10622

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8304

AN:

67990

Other (OTH)

AF:

0.107

AC:

226

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

820

1640

2459

3279

4099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.113

Hom.:

1173

Bravo

AF:

0.115

Asia WGS

AF:

0.0760

AC:

264

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.47

PhyloP100

-0.69

BranchPoint Hunter

0.0

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