rs1538660

Positions:

chr9-108879545-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003640.5(ELP1):c.3473C>T(p.Pro1158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,611,346 control chromosomes in the GnomAD database, including 28,307 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4006 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24301 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 3.18

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:

ELP1 (HGNC:):

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=0.004501313).

BP6

Variant 9-108879545-G-A is Benign according to our data. Variant chr9-108879545-G-A is described in ClinVar as [Benign]. Clinvar id is 259113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-108879545-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP1	NM_003640.5 linkuse as main transcript	c.3473C>T	p.Pro1158Leu	missense_variant	33/37	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516
ELP1	NM_001318360.2 linkuse as main transcript	c.3131C>T	p.Pro1044Leu	missense_variant	33/37		NP_001305289.1	O95163A0A6Q8PGW3B4E3I9
ELP1	NM_001330749.2 linkuse as main transcript	c.2426C>T	p.Pro809Leu	missense_variant	31/35		NP_001317678.1	F5H2T0B3KNB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 linkuse as main transcript	c.3473C>T	p.Pro1158Leu	missense_variant	33/37	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.217

AC:

33017

AN:

151832

Hom.:

4003

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.223

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.194

AC:

48749

AN:

250972

Hom.:

5125

AF XY:

0.194

AC XY:

26290

AN XY:

135652

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.287

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.177

AC:

258332

AN:

1459392

Hom.:

24301

Cov.:

AF XY:

0.179

AC XY:

129759

AN XY:

726126

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.221

Gnomad4 EAS exome

AF:

0.323

Gnomad4 SAS exome

AF:

0.223

Gnomad4 FIN exome

AF:

0.188

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.190

GnomAD4 genome

AF:

0.217

AC:

33039

AN:

151954

Hom.:

4006

Cov.:

AF XY:

0.218

AC XY:

16182

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.223

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.180

Hom.:

5911

Bravo

AF:

0.220

TwinsUK

AF:

0.160

AC:

594

ALSPAC

AF:

0.172

AC:

663

ESP6500AA

AF:

0.303

AC:

1333

ESP6500EA

AF:

0.165

AC:

1423

ExAC

AF:

0.198

AC:

24067

Asia WGS

AF:

0.274

AC:

951

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:3

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	GeneDx	Mar 03, 2015	- -
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	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

L;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.045

Sift

Benign

0.72

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.0020

B;.

Vest4

0.084

MPC

0.074

ClinPred

0.0018

GERP RS

3.0

Varity_R

0.018

gMVP

0.43

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