rs2230794

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.2490A>G(p.Ile830Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0546 in 1,613,950 control chromosomes in the GnomAD database, including 3,369 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 (★★).

Frequency

Genomes: 𝑓 0.053 ( 322 hom., cov: 32)

Exomes 𝑓: 0.055 ( 3047 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0970

Publications

29 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: Orphanet, G2P
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=0.0014864802).

BP6

Variant 9-108897159-T-C is Benign according to our data. Variant chr9-108897159-T-C is described in ClinVar as Benign. ClinVar VariationId is 137579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003640.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELP1	NM_003640.5	MANE Select	c.2490A>G	p.Ile830Met	missense	Exon 23 of 37	NP_003631.2
ELP1	NM_001318360.2		c.2148A>G	p.Ile716Met	missense	Exon 23 of 37	NP_001305289.1	A0A6Q8PGW3
ELP1	NM_001330749.2		c.1443A>G	p.Ile481Met	missense	Exon 21 of 35	NP_001317678.1	F5H2T0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELP1	ENST00000374647.10	TSL:1 MANE Select	c.2490A>G	p.Ile830Met	missense	Exon 23 of 37	ENSP00000363779.5	O95163
ELP1	ENST00000537196.1	TSL:1	c.1443A>G	p.Ile481Met	missense	Exon 16 of 30	ENSP00000439367.1	F5H2T0
ELP1	ENST00000495759.6	TSL:1	n.*1100A>G		non_coding_transcript_exon	Exon 17 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes

AF:

0.0525

AC:

7987

AN:

152136

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.0565

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0508

Gnomad OTH

AF:

0.0583

GnomAD2 exomes

AF:

0.0744

AC:

18706

AN:

251332

AF XY:

0.0684

show subpopulations

Gnomad AFR exome

AF:

0.0130

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.0195

Gnomad EAS exome

AF:

0.107

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.0464

Gnomad OTH exome

AF:

0.0680

GnomAD4 exome

AF:

0.0548

AC:

80079

AN:

1461694

Hom.:

3047

Cov.:

AF XY:

0.0533

AC XY:

38787

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.0125

AC:

418

AN:

33476

American (AMR)

AF:

0.195

AC:

8709

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0199

AC:

521

AN:

26134

East Asian (EAS)

AF:

0.114

AC:

4520

AN:

39694

South Asian (SAS)

AF:

0.0448

AC:

3866

AN:

86248

European-Finnish (FIN)

AF:

0.0956

AC:

5107

AN:

53418

Middle Eastern (MID)

AF:

0.0338

AC:

195

AN:

5768

European-Non Finnish (NFE)

AF:

0.0481

AC:

53523

AN:

1111840

Other (OTH)

AF:

0.0533

AC:

3220

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

4456

8912

13368

17824

22280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2172

4344

6516

8688

10860

<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:

0.0525

AC:

7995

AN:

152256

Hom.:

322

Cov.:

AF XY:

0.0562

AC XY:

4187

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0145

AC:

602

AN:

41568

American (AMR)

AF:

0.118

AC:

1811

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0173

AC:

AN:

3470

East Asian (EAS)

AF:

0.111

AC:

572

AN:

5174

South Asian (SAS)

AF:

0.0557

AC:

268

AN:

4808

European-Finnish (FIN)

AF:

0.101

AC:

1067

AN:

10600

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0507

AC:

3452

AN:

68020

Other (OTH)

AF:

0.0572

AC:

121

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

381

762

1143

1524

1905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0494

Hom.:

591

Bravo

AF:

0.0548

TwinsUK

AF:

0.0558

AC:

207

ALSPAC

AF:

0.0470

AC:

181

ESP6500AA

AF:

0.0157

AC:

ESP6500EA

AF:

0.0467

AC:

402

ExAC

AF:

0.0672

AC:

8157

Asia WGS

AF:

0.0940

AC:

324

AN:

3478

EpiCase

AF:

0.0444

EpiControl

AF:

0.0453

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Familial dysautonomia (2)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.037

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.74

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

-0.097

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.26

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.57

Vest4

0.14

MPC

0.091

ClinPred

0.0079

GERP RS

-1.9

Varity_R

0.054

gMVP

0.21

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over