9-108898571-C-T

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.2294G>A(p.Gly765Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,601,350 control chromosomes in the GnomAD database, including 35,513 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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. G765G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.26 ( 5950 hom., cov: 32)

Exomes 𝑓: 0.20 ( 29563 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.95

Publications

35 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=0.010578513).

BP6

Variant 9-108898571-C-T is Benign according to our data. Variant chr9-108898571-C-T is described in ClinVar as Benign. ClinVar VariationId is 137577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5 link	c.2294G>A	p.Gly765Glu	missense_variant	Exon 22 of 37	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516
ELP1	NM_001318360.2 link	c.1952G>A	p.Gly651Glu	missense_variant	Exon 22 of 37		NP_001305289.1	O95163A0A6Q8PGW3B4E3I9
ELP1	NM_001330749.2 link	c.1247G>A	p.Gly416Glu	missense_variant	Exon 20 of 35		NP_001317678.1	F5H2T0B3KNB2
ELP1	XM_047423991.1 link	c.2294G>A	p.Gly765Glu	missense_variant	Exon 22 of 25		XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 link	c.2294G>A	p.Gly765Glu	missense_variant	Exon 22 of 37	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.259

AC:

39333

AN:

151928

Hom.:

5943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.238

Gnomad ASJ

AF:

0.0741

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.143

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.221

AC:

55278

AN:

250044

AF XY:

0.213

show subpopulations

Gnomad AFR exome

AF:

0.423

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.0837

Gnomad EAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.195

GnomAD4 exome

AF:

0.195

AC:

283107

AN:

1449300

Hom.:

29563

Cov.:

AF XY:

0.194

AC XY:

139959

AN XY:

721712

show subpopulations

African (AFR)

AF:

0.420

AC:

13864

AN:

33012

American (AMR)

AF:

0.282

AC:

12598

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.0836

AC:

2180

AN:

26078

East Asian (EAS)

AF:

0.279

AC:

11004

AN:

39508

South Asian (SAS)

AF:

0.195

AC:

16765

AN:

85920

European-Finnish (FIN)

AF:

0.228

AC:

12137

AN:

53260

Middle Eastern (MID)

AF:

0.127

AC:

685

AN:

5380

European-Non Finnish (NFE)

AF:

0.184

AC:

202169

AN:

1101570

Other (OTH)

AF:

0.195

AC:

11705

AN:

59934

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

10818

21636

32453

43271

54089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7278

14556

21834

29112

36390

<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:

0.259

AC:

39376

AN:

152050

Hom.:

5950

Cov.:

AF XY:

0.260

AC XY:

19301

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.413

AC:

17095

AN:

41440

American (AMR)

AF:

0.238

AC:

3643

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0741

AC:

257

AN:

3470

East Asian (EAS)

AF:

0.271

AC:

1401

AN:

5170

South Asian (SAS)

AF:

0.216

AC:

1042

AN:

4820

European-Finnish (FIN)

AF:

0.238

AC:

2520

AN:

10574

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12657

AN:

67974

Other (OTH)

AF:

0.227

AC:

480

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1413

2826

4240

5653

7066

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.209

Hom.:

9307

Bravo

AF:

0.271

TwinsUK

AF:

0.189

AC:

702

ALSPAC

AF:

0.197

AC:

758

ESP6500AA

AF:

0.414

AC:

1820

ESP6500EA

AF:

0.182

AC:

1566

ExAC

AF:

0.224

AC:

27142

Asia WGS

AF:

0.263

AC:

912

AN:

3472

EpiCase

AF:

0.174

EpiControl

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:4

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. -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 20, 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. -

Jul 08, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.056

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.16

DEOGEN2

Benign

0.019

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.15

T;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.1

N;.

PhyloP100

1.9

PrimateAI

Uncertain

0.59

PROVEAN

Benign

2.8

N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.074

MPC

0.091

ClinPred

0.0027

GERP RS

4.0

Varity_R

0.10

gMVP

0.16

Mutation Taster

=99/1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over