9-108889340-A-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.3214T>A(p.Cys1072Ser) variant causes a missense change. The variant allele was found at a frequency of 0.181 in 1,613,288 control chromosomes in the GnomAD database, including 28,322 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C1072F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.22 ( 4012 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24310 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.72

Publications

44 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=0.003656298).

BP6

Variant 9-108889340-A-T is Benign according to our data. Variant chr9-108889340-A-T is described in ClinVar as Benign. ClinVar VariationId is 259112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5 link	c.3214T>A	p.Cys1072Ser	missense_variant	Exon 29 of 37	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516
ELP1	NM_001318360.2 link	c.2872T>A	p.Cys958Ser	missense_variant	Exon 29 of 37		NP_001305289.1	O95163A0A6Q8PGW3B4E3I9
ELP1	NM_001330749.2 link	c.2167T>A	p.Cys723Ser	missense_variant	Exon 27 of 35		NP_001317678.1	F5H2T0B3KNB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 link	c.3214T>A	p.Cys1072Ser	missense_variant	Exon 29 of 37	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33060

AN:

151902

Hom.:

4009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.199

GnomAD2 exomes

AF:

0.194

AC:

48834

AN:

251268

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.288

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.177

AC:

259093

AN:

1461268

Hom.:

24310

Cov.:

AF XY:

0.179

AC XY:

130100

AN XY:

726934

show subpopulations

African (AFR)

AF:

0.325

AC:

10876

AN:

33464

American (AMR)

AF:

0.147

AC:

6569

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

5825

AN:

26132

East Asian (EAS)

AF:

0.323

AC:

12834

AN:

39692

South Asian (SAS)

AF:

0.223

AC:

19236

AN:

86242

European-Finnish (FIN)

AF:

0.188

AC:

10032

AN:

53412

Middle Eastern (MID)

AF:

0.186

AC:

1070

AN:

5768

European-Non Finnish (NFE)

AF:

0.163

AC:

181163

AN:

1111470

Other (OTH)

AF:

0.190

AC:

11488

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

11115

22230

33344

44459

55574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6554

13108

19662

26216

32770

<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:

0.218

AC:

33083

AN:

152020

Hom.:

4012

Cov.:

AF XY:

0.218

AC XY:

16215

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.319

AC:

13222

AN:

41436

American (AMR)

AF:

0.160

AC:

2447

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

783

AN:

3468

East Asian (EAS)

AF:

0.293

AC:

1516

AN:

5170

South Asian (SAS)

AF:

0.229

AC:

1104

AN:

4814

European-Finnish (FIN)

AF:

0.183

AC:

1939

AN:

10572

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11342

AN:

67970

Other (OTH)

AF:

0.197

AC:

417

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1323

2645

3968

5290

6613

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:

0.182

Hom.:

2075

Bravo

AF:

0.220

TwinsUK

AF:

0.160

AC:

595

ALSPAC

AF:

0.173

AC:

665

ESP6500AA

AF:

0.304

AC:

1341

ESP6500EA

AF:

0.165

AC:

1423

ExAC

AF:

0.198

AC:

24083

Asia WGS

AF:

0.274

AC:

951

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:4

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 10, 2017

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 13, 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. -

not provided

Benign:4

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

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 17, 2017

Women's Health and Genetics/Laboratory Corporation of America, 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

0.17

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.083

T;T

Eigen

Benign

-0.087

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.19

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

N;.

PhyloP100

6.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.0

B;.

Vest4

0.17

MutPred

0.50

Gain of disorder (P = 0.001);.;

MPC

0.086

ClinPred

0.020

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.55

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