rs1538660

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003640.5(ELP1):c.3473C>T(p.Pro1158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,611,346 control chromosomes in the GnomAD database, including 28,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1158P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.22 ( 4006 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24301 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.18

Publications

40 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004501313).

BP6

Variant 9-108879545-G-A is Benign according to our data. Variant chr9-108879545-G-A is described in ClinVar as Benign. ClinVar VariationId is 259113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5 link	c.3473C>T	p.Pro1158Leu	missense_variant	Exon 33 of 37	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516
ELP1	NM_001318360.2 link	c.3131C>T	p.Pro1044Leu	missense_variant	Exon 33 of 37		NP_001305289.1	O95163A0A6Q8PGW3B4E3I9
ELP1	NM_001330749.2 link	c.2426C>T	p.Pro809Leu	missense_variant	Exon 31 of 35		NP_001317678.1	F5H2T0B3KNB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 link	c.3473C>T	p.Pro1158Leu	missense_variant	Exon 33 of 37	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33017

AN:

151832

Hom.:

4003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.199

GnomAD2 exomes

AF:

0.194

AC:

48749

AN:

250972

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.287

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.177

AC:

258332

AN:

1459392

Hom.:

24301

Cov.:

AF XY:

0.179

AC XY:

129759

AN XY:

726126

show subpopulations

African (AFR)

AF:

0.323

AC:

10799

AN:

33412

American (AMR)

AF:

0.147

AC:

6574

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.221

AC:

5765

AN:

26120

East Asian (EAS)

AF:

0.323

AC:

12823

AN:

39676

South Asian (SAS)

AF:

0.223

AC:

19213

AN:

86214

European-Finnish (FIN)

AF:

0.188

AC:

10032

AN:

53398

Middle Eastern (MID)

AF:

0.185

AC:

1065

AN:

5760

European-Non Finnish (NFE)

AF:

0.163

AC:

180606

AN:

1109802

Other (OTH)

AF:

0.190

AC:

11455

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

10312

20624

30936

41248

51560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6522

13044

19566

26088

32610

<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:

0.217

AC:

33039

AN:

151954

Hom.:

4006

Cov.:

AF XY:

0.218

AC XY:

16182

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.318

AC:

13170

AN:

41438

American (AMR)

AF:

0.161

AC:

2462

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

772

AN:

3466

East Asian (EAS)

AF:

0.293

AC:

1505

AN:

5140

South Asian (SAS)

AF:

0.229

AC:

1101

AN:

4814

European-Finnish (FIN)

AF:

0.184

AC:

1942

AN:

10536

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11358

AN:

67974

Other (OTH)

AF:

0.197

AC:

416

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1285

2569

3854

5138

6423

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.188

Hom.:

9054

Bravo

AF:

0.220

TwinsUK

AF:

0.160

AC:

594

ALSPAC

AF:

0.172

AC:

663

ESP6500AA

AF:

0.303

AC:

1333

ESP6500EA

AF:

0.165

AC:

1423

ExAC

AF:

0.198

AC:

24067

Asia WGS

AF:

0.274

AC:

951

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:3

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. -

May 10, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

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

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

L;.

PhyloP100

3.2

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.045

Sift

Benign

0.72

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.0020

B;.

Vest4

0.084

MPC

0.074

ClinPred

0.0018

GERP RS

3.0

Varity_R

0.018

gMVP

0.43

Mutation Taster

=98/2

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