Genetic Variant ELN:c.1096+49_1096+50dupGT (chr7-74053320-C-CTG) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_000501.4(ELN):c.1096+49_1096+50dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.13 ( 1264 hom., cov: 0)

Exomes 𝑓: 0.11 ( 4 hom. )

Consequence

ELN
NM_000501.4 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:2

Conservation

PhyloP100: 0.780

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 7-74053320-C-CTG is Benign according to our data. Variant chr7-74053320-C-CTG is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 360643.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=4, Benign=2}.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 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+50dupGT		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+11_1096+12insTG		intron_variant	Intron 18 of 32	1	NM_000501.4	ENSP00000252034.7		P15502-2

Frequencies

GnomAD3 genomes

AF:

0.134

AC:

19364

AN:

144016

Hom.:

1263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.113

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.0945

Gnomad SAS

AF:

0.132

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.197

Gnomad NFE

AF:

0.151

Gnomad OTH

AF:

0.146

GnomAD4 exome

AF:

0.113

AC:

154927

AN:

1376902

Hom.:

Cov.:

AF XY:

0.112

AC XY:

76710

AN XY:

682936

show subpopulations

Gnomad4 AFR exome

AF:

0.0989

Gnomad4 AMR exome

AF:

0.0798

Gnomad4 ASJ exome

AF:

0.127

Gnomad4 EAS exome

AF:

0.0588

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.0845

Gnomad4 NFE exome

AF:

0.117

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.134

AC:

19374

AN:

144118

Hom.:

1264

Cov.:

AF XY:

0.131

AC XY:

9130

AN XY:

69874

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.113

Gnomad4 ASJ

AF:

0.170

Gnomad4 EAS

AF:

0.0939

Gnomad4 SAS

AF:

0.133

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.151

Gnomad4 OTH

AF:

0.144

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Supravalvar aortic stenosis

Uncertain:2Benign:1

Jan 30, 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

- -

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:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

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

- -

not provided

Benign:1

Aug 26, 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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

7-74053320-CTGTGTGTGTGTGTGTGTGTGTGTG-CTGTGTGTGTGTGTGTGTGTGTGTGTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over