9-108898571-C-T

Position:

chr9-108898571-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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=0.010578513).

BP6

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

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/exons	MANE	Protein
ELP1	NM_003640.5 linkuse as main transcript	c.2294G>A	p.Gly765Glu	missense_variant	22/37	ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2 linkuse as main transcript	c.1952G>A	p.Gly651Glu	missense_variant	22/37		NP_001305289.1
ELP1	NM_001330749.2 linkuse as main transcript	c.1247G>A	p.Gly416Glu	missense_variant	20/35		NP_001317678.1
ELP1	XM_047423991.1 linkuse as main transcript	c.2294G>A	p.Gly765Glu	missense_variant	22/25		XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 linkuse as main transcript	c.2294G>A	p.Gly765Glu	missense_variant	22/37	1	NM_003640.5	ENSP00000363779	P1

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

GnomAD3 exomes

AF:

0.221

AC:

55278

AN:

250044

Hom.:

6712

AF XY:

0.213

AC XY:

28751

AN XY:

135176

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 SAS exome

AF:

0.198

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

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.0836

Gnomad4 EAS exome

AF:

0.279

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.184

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.259

AC:

39376

AN:

152050

Hom.:

5950

Cov.:

AF XY:

0.260

AC XY:

19301

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.238

Gnomad4 ASJ

AF:

0.0741

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.238

Gnomad4 NFE

AF:

0.186

Gnomad4 OTH

AF:

0.227

Alfa

AF:

0.195

Hom.:

5482

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

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 10, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 08, 2014	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 20, 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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

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

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

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;.

MutationTaster

Benign

1.0

P;P

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

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

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