9-108891294-C-G

Position:

chr9-108891294-C-G

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000374647.10(ELP1):c.3069G>C(p.Leu1023=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,613,932 control chromosomes in the GnomAD database, including 151,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L1023L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.35 ( 10889 hom., cov: 33)

Exomes 𝑓: 0.43 ( 140588 hom. )

Consequence

ELP1
ENST00000374647.10 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.25

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 9-108891294-C-G is Benign according to our data. Variant chr9-108891294-C-G is described in ClinVar as [Benign]. Clinvar id is 259111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-108891294-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 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.3069G>C	p.Leu1023=	synonymous_variant	28/37	ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2 linkuse as main transcript	c.2727G>C	p.Leu909=	synonymous_variant	28/37		NP_001305289.1
ELP1	NM_001330749.2 linkuse as main transcript	c.2022G>C	p.Leu674=	synonymous_variant	26/35		NP_001317678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 linkuse as main transcript	c.3069G>C	p.Leu1023=	synonymous_variant	28/37	1	NM_003640.5	ENSP00000363779	P1

Frequencies

GnomAD3 genomes

AF:

0.347

AC:

52791

AN:

152014

Hom.:

10883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.447

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.398

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.453

Gnomad OTH

AF:

0.396

GnomAD3 exomes

AF:

0.402

AC:

100781

AN:

250962

Hom.:

21422

AF XY:

0.403

AC XY:

54612

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.0943

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.452

Gnomad SAS exome

AF:

0.314

Gnomad FIN exome

AF:

0.403

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.433

AC:

633540

AN:

1461798

Hom.:

140588

Cov.:

AF XY:

0.431

AC XY:

313407

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0909

Gnomad4 AMR exome

AF:

0.419

Gnomad4 ASJ exome

AF:

0.490

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.403

Gnomad4 NFE exome

AF:

0.454

Gnomad4 OTH exome

AF:

0.426

GnomAD4 genome

AF:

0.347

AC:

52804

AN:

152134

Hom.:

10889

Cov.:

AF XY:

0.347

AC XY:

25765

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.103

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.448

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.398

Gnomad4 NFE

AF:

0.453

Gnomad4 OTH

AF:

0.401

Alfa

AF:

0.338

Hom.:

1672

Bravo

AF:

0.341

Asia WGS

AF:

0.347

AC:

1207

AN:

3478

EpiCase

AF:

0.447

EpiControl

AF:

0.457

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 10, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

7.8

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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