NM_000501.4:c.1414+24C>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.1414+24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,611,374 control chromosomes in the GnomAD database, including 259,425 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 28146 hom., cov: 31)

Exomes 𝑓: 0.56 ( 231279 hom. )

Consequence

ELN
NM_000501.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.37

Publications

13 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

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 7-74057720-C-T is Benign according to our data. Variant chr7-74057720-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELN	NM_000501.4 link	c.1414+24C>T		intron_variant	Intron 22 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.1414+24C>T		intron_variant	Intron 22 of 32	1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.604

AC:

91768

AN:

151840

Hom.:

28115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.694

Gnomad AMI

AF:

0.572

Gnomad AMR

AF:

0.576

Gnomad ASJ

AF:

0.519

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.606

Gnomad MID

AF:

0.601

Gnomad NFE

AF:

0.549

Gnomad OTH

AF:

0.576

GnomAD2 exomes

AF:

0.590

AC:

147337

AN:

249772

AF XY:

0.592

show subpopulations

Gnomad AFR exome

AF:

0.699

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.522

Gnomad EAS exome

AF:

0.712

Gnomad FIN exome

AF:

0.598

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.560

AC:

817610

AN:

1459414

Hom.:

231279

Cov.:

AF XY:

0.564

AC XY:

409615

AN XY:

726036

show subpopulations

African (AFR)

AF:

0.698

AC:

23322

AN:

33406

American (AMR)

AF:

0.574

AC:

25655

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.521

AC:

13605

AN:

26126

East Asian (EAS)

AF:

0.704

AC:

27936

AN:

39694

South Asian (SAS)

AF:

0.673

AC:

57996

AN:

86166

European-Finnish (FIN)

AF:

0.601

AC:

32081

AN:

53414

Middle Eastern (MID)

AF:

0.585

AC:

2720

AN:

4646

European-Non Finnish (NFE)

AF:

0.540

AC:

599767

AN:

1111052

Other (OTH)

AF:

0.573

AC:

34528

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

18026

36052

54079

72105

90131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17114

34228

51342

68456

85570

<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:

0.604

AC:

91837

AN:

151960

Hom.:

28146

Cov.:

AF XY:

0.609

AC XY:

45210

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.694

AC:

28782

AN:

41468

American (AMR)

AF:

0.577

AC:

8811

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.519

AC:

1796

AN:

3460

East Asian (EAS)

AF:

0.701

AC:

3593

AN:

5124

South Asian (SAS)

AF:

0.680

AC:

3274

AN:

4814

European-Finnish (FIN)

AF:

0.606

AC:

6403

AN:

10570

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.549

AC:

37279

AN:

67936

Other (OTH)

AF:

0.570

AC:

1202

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1842

3685

5527

7370

9212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

764

1528

2292

3056

3820

<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:

0.565

Hom.:

35034

Bravo

AF:

0.606

Asia WGS

AF:

0.599

AC:

2083

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Cutis laxa, autosomal dominant 1

Benign:1

Jul 30, 2021

Genome-Nilou Lab

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

0.11

(source)

DANN

Benign

0.63

PhyloP100

-1.4

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