rs34852121

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001278939.2(ELN):c.2137G>A(p.Gly713Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,613,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

ELN
NM_001278939.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 4.81

Publications

7 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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278939.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ELN	NM_000501.4	MANE Select	c.1951G>A	p.Gly651Arg	missense	Exon 29 of 33	NP_000492.2
ELN	NM_001278939.2		c.2137G>A	p.Gly713Arg	missense	Exon 30 of 34	NP_001265868.1
ELN	NM_001278915.2		c.1969G>A	p.Gly657Arg	missense	Exon 29 of 33	NP_001265844.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ELN	ENST00000252034.12	TSL:1 MANE Select	c.1951G>A	p.Gly651Arg	missense	Exon 29 of 33	ENSP00000252034.7
ELN	ENST00000380562.8	TSL:1	c.1969G>A	p.Gly657Arg	missense	Exon 29 of 33	ENSP00000369936.4
ELN	ENST00000458204.5	TSL:1	c.1921G>A	p.Gly641Arg	missense	Exon 28 of 32	ENSP00000403162.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000716

AC:

AN:

251484

AF XY:

0.0000515

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000602

AC:

AN:

1461518

Hom.:

Cov.:

AF XY:

0.0000646

AC XY:

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.000168

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

1111736

Other (OTH)

AF:

0.0000331

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000460

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41446

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000772

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Supravalvar aortic stenosis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.13

Eigen

Benign

0.025

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.45

M_CAP

Pathogenic

0.41

MetaRNN

Uncertain

0.73

MetaSVM

Benign

-0.81

MutationAssessor

Benign

2.0

PhyloP100

4.8

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.70

MutPred

0.31

Gain of methylation at G641 (P = 0.0046)

MVP

0.82

MPC

0.22

ClinPred

0.17

GERP RS

3.0

Varity_R

0.093

gMVP

0.81

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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