chr9-108889340-A-T

Variant names:

Variant summary

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

The NM_003640.5(ELP1):c.3214T>A(p.Cys1072Ser) variant causes a missense change. The variant allele was found at a frequency of 0.181 in 1,613,288 control chromosomes in the GnomAD database, including 28,322 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4012 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24310 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.72

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=0.003656298).

BP6

Variant 9-108889340-A-T is Benign according to our data. Variant chr9-108889340-A-T is described in ClinVar as [Benign]. Clinvar id is 259112.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-108889340-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5 link	c.3214T>A	p.Cys1072Ser	missense_variant	Exon 29 of 37	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516
ELP1	NM_001318360.2 link	c.2872T>A	p.Cys958Ser	missense_variant	Exon 29 of 37		NP_001305289.1	O95163A0A6Q8PGW3B4E3I9
ELP1	NM_001330749.2 link	c.2167T>A	p.Cys723Ser	missense_variant	Exon 27 of 35		NP_001317678.1	F5H2T0B3KNB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 link	c.3214T>A	p.Cys1072Ser	missense_variant	Exon 29 of 37	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33060

AN:

151902

Hom.:

4009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.319

Gnomad AMI

AF:

0.275

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.294

Gnomad SAS

AF:

0.230

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.199

GnomAD3 exomes

AF:

0.194

AC:

48834

AN:

251268

Hom.:

5162

AF XY:

0.194

AC XY:

26341

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.320

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.225

Gnomad EAS exome

AF:

0.288

Gnomad SAS exome

AF:

0.228

Gnomad FIN exome

AF:

0.187

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.177

AC:

259093

AN:

1461268

Hom.:

24310

Cov.:

AF XY:

0.179

AC XY:

130100

AN XY:

726934

show subpopulations

Gnomad4 AFR exome

AF:

0.325

Gnomad4 AMR exome

AF:

0.147

Gnomad4 ASJ exome

AF:

0.223

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:

0.218

AC:

33083

AN:

152020

Hom.:

4012

Cov.:

AF XY:

0.218

AC XY:

16215

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.319

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.229

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.167

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.182

Hom.:

2075

Bravo

AF:

0.220

TwinsUK

AF:

0.160

AC:

595

ALSPAC

AF:

0.173

AC:

665

ESP6500AA

AF:

0.304

AC:

1341

ESP6500EA

AF:

0.165

AC:

1423

ExAC

AF:

0.198

AC:

24083

Asia WGS

AF:

0.274

AC:

951

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial dysautonomia

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 10, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:4

Jul 17, 2017

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.083

T;T

Eigen

Benign

-0.087

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.19

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

N;.

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.11

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.0

B;.

Vest4

0.17

MutPred

0.50

Gain of disorder (P = 0.001);.;

MPC

0.086

ClinPred

0.020

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.37

gMVP

0.55

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