rs79596285

Positions:

chr9-108879526-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000374647.10(ELP1):c.3492C>T(p.Asp1164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,613,992 control chromosomes in the GnomAD database, including 1,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 114 hom., cov: 33)

Exomes 𝑓: 0.0086 ( 897 hom. )

Consequence

ELP1
ENST00000374647.10 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.121

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 9-108879526-G-A is Benign according to our data. Variant chr9-108879526-G-A is described in ClinVar as [Benign]. Clinvar id is 364557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.121 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0853 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.3492C>T	p.Asp1164=	synonymous_variant	33/37	ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2 linkuse as main transcript	c.3150C>T	p.Asp1050=	synonymous_variant	33/37		NP_001305289.1
ELP1	NM_001330749.2 linkuse as main transcript	c.2445C>T	p.Asp815=	synonymous_variant	31/35		NP_001317678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 linkuse as main transcript	c.3492C>T	p.Asp1164=	synonymous_variant	33/37	1	NM_003640.5	ENSP00000363779	P1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2304

AN:

152140

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0885

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.0447

Gnomad SAS

AF:

0.00437

Gnomad FIN

AF:

0.0416

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00138

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.0331

AC:

8326

AN:

251308

Hom.:

706

AF XY:

0.0267

AC XY:

3627

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0446

Gnomad SAS exome

AF:

0.00199

Gnomad FIN exome

AF:

0.0404

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.0223

GnomAD4 exome

AF:

0.00864

AC:

12636

AN:

1461734

Hom.:

897

Cov.:

AF XY:

0.00773

AC XY:

5623

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00209

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.0464

Gnomad4 SAS exome

AF:

0.00212

Gnomad4 FIN exome

AF:

0.0364

Gnomad4 NFE exome

AF:

0.000456

Gnomad4 OTH exome

AF:

0.00815

GnomAD4 genome

AF:

0.0152

AC:

2317

AN:

152258

Hom.:

114

Cov.:

AF XY:

0.0179

AC XY:

1336

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00318

Gnomad4 AMR

AF:

0.0892

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.0448

Gnomad4 SAS

AF:

0.00458

Gnomad4 FIN

AF:

0.0416

Gnomad4 NFE

AF:

0.00138

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00428

Hom.:

Bravo

AF:

0.0218

Asia WGS

AF:

0.0290

AC:

101

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 25, 2016	Variant summary: The IKBKAP c.3492C>T (p.Asp1164Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a disease-causing outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 3138/121288 control chromosomes (271 homozygotes) at a frequency of 0.0258723, which is approximately 14 times the estimated maximal expected allele frequency of a pathogenic IKBKAP variant (0.001838), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign. -
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	-	- -

Familial dysautonomia

Benign:2

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. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	May 10, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

5.5

DANN

Benign

0.58

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