7-74028150-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000380562.8(ELN):c.-38C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0141 in 1,393,342 control chromosomes in the GnomAD database, including 360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 18 hom., cov: 31)

Exomes 𝑓: 0.015 ( 342 hom. )

Consequence

ELN
ENST00000380562.8 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.34

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: 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

ELN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 7-74028150-C-T is Benign according to our data. Variant chr7-74028150-C-T is described in ClinVar as Benign. ClinVar VariationId is 213168.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0798 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380562.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ELN	NM_000501.4	MANE Select	c.-38C>T	upstream_gene	N/A	NP_000492.2	P15502-2
ELN	NM_001278939.2		c.-38C>T	upstream_gene	N/A	NP_001265868.1	P15502-3
ELN	NM_001278915.2		c.-38C>T	upstream_gene	N/A	NP_001265844.1	P15502-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ELN	ENST00000380562.8	TSL:1	c.-38C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 33	ENSP00000369936.4	P15502-1
ELN	ENST00000380562.8	TSL:1	c.-38C>T	5_prime_UTR	Exon 1 of 33	ENSP00000369936.4	P15502-1
ELN	ENST00000869821.1		c.-38C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 33	ENSP00000539880.1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1497

AN:

142404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0117

Gnomad ASJ

AF:

0.0168

Gnomad EAS

AF:

0.0449

Gnomad SAS

AF:

0.0869

Gnomad FIN

AF:

0.00133

Gnomad MID

AF:

0.0300

Gnomad NFE

AF:

0.00824

Gnomad OTH

AF:

0.0125

GnomAD2 exomes

AF:

0.0184

AC:

4380

AN:

237612

AF XY:

0.0215

show subpopulations

Gnomad AFR exome

AF:

0.00238

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.0323

Gnomad FIN exome

AF:

0.00127

Gnomad NFE exome

AF:

0.00875

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0145

AC:

18195

AN:

1250810

Hom.:

342

Cov.:

AF XY:

0.0169

AC XY:

10447

AN XY:

619012

show subpopulations

African (AFR)

AF:

0.00390

AC:

107

AN:

27424

American (AMR)

AF:

0.0128

AC:

486

AN:

38104

Ashkenazi Jewish (ASJ)

AF:

0.0228

AC:

424

AN:

18592

East Asian (EAS)

AF:

0.0679

AC:

1516

AN:

22314

South Asian (SAS)

AF:

0.0736

AC:

6154

AN:

83660

European-Finnish (FIN)

AF:

0.00227

AC:

AN:

33418

Middle Eastern (MID)

AF:

0.0445

AC:

210

AN:

4720

European-Non Finnish (NFE)

AF:

0.00851

AC:

8307

AN:

975860

Other (OTH)

AF:

0.0196

AC:

915

AN:

46718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

914

1827

2741

3654

4568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.0105

AC:

1499

AN:

142532

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

824

AN XY:

69050

show subpopulations

African (AFR)

AF:

0.00383

AC:

151

AN:

39448

American (AMR)

AF:

0.0117

AC:

165

AN:

14126

Ashkenazi Jewish (ASJ)

AF:

0.0168

AC:

AN:

3332

East Asian (EAS)

AF:

0.0447

AC:

187

AN:

4184

South Asian (SAS)

AF:

0.0873

AC:

356

AN:

4078

European-Finnish (FIN)

AF:

0.00133

AC:

AN:

9048

Middle Eastern (MID)

AF:

0.0324

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.00824

AC:

537

AN:

65150

Other (OTH)

AF:

0.0129

AC:

AN:

2020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

144

215

287

359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00729

Hom.:

Bravo

AF:

0.00926

Asia WGS

AF:

0.0560

AC:

195

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cutis laxa, autosomal dominant (1)

not provided (1)

Supravalvar aortic stenosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.97

PhyloP100

2.3

PromoterAI

-0.043

Neutral

(source)

Mutation Taster

=299/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over