rs2230794

Positions:

chr9-108897159-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 137579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-108897159-T-C is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ELP1	NM_003640.5 linkuse as main transcript	c.2490A>G	p.Ile830Met	missense_variant	23/37	ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2 linkuse as main transcript	c.2148A>G	p.Ile716Met	missense_variant	23/37		NP_001305289.1
ELP1	NM_001330749.2 linkuse as main transcript	c.1443A>G	p.Ile481Met	missense_variant	21/35		NP_001317678.1
ELP1	XM_047423991.1 linkuse as main transcript	c.2490A>G	p.Ile830Met	missense_variant	23/25		XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 linkuse as main transcript	c.2490A>G	p.Ile830Met	missense_variant	23/37	1	NM_003640.5	ENSP00000363779	P1

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

GnomAD3 exomes

AF:

0.0744

AC:

18706

AN:

251332

Hom.:

1183

AF XY:

0.0684

AC XY:

9296

AN XY:

135828

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 SAS exome

AF:

0.0454

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

Gnomad4 AFR exome

AF:

0.0125

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.0448

Gnomad4 FIN exome

AF:

0.0956

Gnomad4 NFE exome

AF:

0.0481

Gnomad4 OTH exome

AF:

0.0533

GnomAD4 genome

AF:

0.0525

AC:

7995

AN:

152256

Hom.:

322

Cov.:

AF XY:

0.0562

AC XY:

4187

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0145

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.0557

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0507

Gnomad4 OTH

AF:

0.0572

Alfa

AF:

0.0504

Hom.:

430

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

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 10, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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 specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2014	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. -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0015

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.74

P;P

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.26

N;N

REVEL

Benign

0.13

Sift

Benign

0.19

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.57

P;.

Vest4

0.14

MPC

0.091

ClinPred

0.0079

GERP RS

-1.9

Varity_R

0.054

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over