NM_003640.5:c.3037G>A

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.3037G>A(p.Gly1013Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00567 in 1,614,072 control chromosomes in the GnomAD database, including 504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1013R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.031 ( 243 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 261 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 7.16

Publications

8 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=0.0024411976).

BP6

Variant 9-108891326-C-T is Benign according to our data. Variant chr9-108891326-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259110.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 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
ELP1	NM_003640.5	MANE Select	c.3037G>A	p.Gly1013Ser	missense	Exon 28 of 37	NP_003631.2
ELP1	NM_001318360.2		c.2695G>A	p.Gly899Ser	missense	Exon 28 of 37	NP_001305289.1
ELP1	NM_001330749.2		c.1990G>A	p.Gly664Ser	missense	Exon 26 of 35	NP_001317678.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ELP1	ENST00000374647.10	TSL:1 MANE Select	c.3037G>A	p.Gly1013Ser	missense	Exon 28 of 37	ENSP00000363779.5
ELP1	ENST00000537196.1	TSL:1	c.1990G>A	p.Gly664Ser	missense	Exon 21 of 30	ENSP00000439367.1
ELP1	ENST00000495759.6	TSL:1	n.*1647G>A		non_coding_transcript_exon	Exon 22 of 31	ENSP00000433514.2

Frequencies

GnomAD3 genomes

AF:

0.0307

AC:

4669

AN:

152104

Hom.:

244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00838

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0225

GnomAD2 exomes

AF:

0.00797

AC:

1998

AN:

250798

AF XY:

0.00560

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00306

AC:

4472

AN:

1461850

Hom.:

261

Cov.:

AF XY:

0.00254

AC XY:

1849

AN XY:

727218

show subpopulations

African (AFR)

AF:

0.115

AC:

3854

AN:

33476

American (AMR)

AF:

0.00425

AC:

190

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00208

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000585

AC:

AN:

1112000

Other (OTH)

AF:

0.00563

AC:

340

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

240

480

719

959

1199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

220

330

440

550

<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:

0.0307

AC:

4676

AN:

152222

Hom.:

243

Cov.:

AF XY:

0.0292

AC XY:

2177

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.108

AC:

4488

AN:

41486

American (AMR)

AF:

0.00830

AC:

127

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68016

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

210

421

631

842

1052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0112

Hom.:

254

Bravo

AF:

0.0361

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.115

AC:

505

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00980

AC:

1190

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Familial dysautonomia (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.3

MutationAssessor

Pathogenic

3.1

PhyloP100

7.2

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.15

Sift

Uncertain

0.026

Sift4G

Benign

0.073

Polyphen

1.0

Vest4

0.58

MVP

0.73

MPC

0.40

ClinPred

0.053

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.44

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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