rs12340246

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003640.5(ELP1):c.819C>T(p.Leu273Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0527 in 1,613,602 control chromosomes in the GnomAD database, including 3,249 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L273L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.051 ( 313 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2936 hom. )

Consequence

ELP1
NM_003640.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.861

Publications

20 publications found

Variant links:

Genes affected

ELP1 (HGNC:5959): (elongator acetyltransferase complex subunit 1) The protein encoded by this gene is a scaffold protein and a regulator for three different kinases involved in proinflammatory signaling. The encoded protein can bind NF-kappa-B-inducing kinase and I-kappa-B kinases through separate domains and assemble them into an active kinase complex. Mutations in this gene have been associated with familial dysautonomia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

ELP1 Gene-Disease associations (from GenCC):

primary dysautonomia
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
Riley-Day syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
medulloblastoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ELP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 9-108917592-G-A is Benign according to our data. Variant chr9-108917592-G-A is described in ClinVar as [Benign]. Clinvar id is 137570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.861 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5 link	c.819C>T	p.Leu273Leu	synonymous_variant	Exon 9 of 37	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516
ELP1	NM_001318360.2 link	c.477C>T	p.Leu159Leu	synonymous_variant	Exon 9 of 37		NP_001305289.1	O95163A0A6Q8PGW3B4E3I9
ELP1	XM_047423991.1 link	c.819C>T	p.Leu273Leu	synonymous_variant	Exon 9 of 25		XP_047279947.1
ELP1	NM_001330749.2 link	c.-229C>T		5_prime_UTR_variant	Exon 7 of 35		NP_001317678.1	F5H2T0B3KNB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 link	c.819C>T	p.Leu273Leu	synonymous_variant	Exon 9 of 37	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.0513

AC:

7806

AN:

152050

Hom.:

311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0144

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.0555

Gnomad FIN

AF:

0.0971

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0485

Gnomad OTH

AF:

0.0566

GnomAD2 exomes

AF:

0.0733

AC:

18430

AN:

251476

AF XY:

0.0673

show subpopulations

Gnomad AFR exome

AF:

0.0125

Gnomad AMR exome

AF:

0.202

Gnomad ASJ exome

AF:

0.0167

Gnomad EAS exome

AF:

0.119

Gnomad FIN exome

AF:

0.0968

Gnomad NFE exome

AF:

0.0444

Gnomad OTH exome

AF:

0.0637

GnomAD4 exome

AF:

0.0528

AC:

77165

AN:

1461432

Hom.:

2936

Cov.:

AF XY:

0.0514

AC XY:

37397

AN XY:

727048

show subpopulations

African (AFR)

AF:

0.0120

AC:

401

AN:

33474

American (AMR)

AF:

0.193

AC:

8652

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0165

AC:

430

AN:

26130

East Asian (EAS)

AF:

0.121

AC:

4819

AN:

39690

South Asian (SAS)

AF:

0.0432

AC:

3727

AN:

86252

European-Finnish (FIN)

AF:

0.0908

AC:

4850

AN:

53418

Middle Eastern (MID)

AF:

0.0333

AC:

192

AN:

5768

European-Non Finnish (NFE)

AF:

0.0459

AC:

51004

AN:

1111608

Other (OTH)

AF:

0.0512

AC:

3090

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

3746

7491

11237

14982

18728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2088

4176

6264

8352

10440

<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:

0.0513

AC:

7810

AN:

152170

Hom.:

313

Cov.:

AF XY:

0.0550

AC XY:

4092

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.0138

AC:

574

AN:

41526

American (AMR)

AF:

0.119

AC:

1818

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0144

AC:

AN:

3470

East Asian (EAS)

AF:

0.120

AC:

619

AN:

5160

South Asian (SAS)

AF:

0.0547

AC:

264

AN:

4828

European-Finnish (FIN)

AF:

0.0971

AC:

1027

AN:

10574

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0485

AC:

3299

AN:

68008

Other (OTH)

AF:

0.0555

AC:

117

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

366

732

1098

1464

1830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0453

Hom.:

445

Bravo

AF:

0.0544

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.0419

EpiControl

AF:

0.0431

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:3

May 10, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 13, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.4

(source)

DANN

Benign

0.69

PhyloP100

0.86

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