rs10979605

Variant names:

• chr9-108901513-C-T
• rs10979605
• NM_003640.5:c.1926G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003640.5(ELP1):​c.1926G>A​(p.Thr642Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0785 in 1,610,884 control chromosomes in the GnomAD database, including 5,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (856 hom., cov: 31)
  • Exomes 𝑓: 0.077 (4889 hom.)
• Consequence: ELP1 NM_003640.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.14
• Publications: 19 publications found

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 Gene-Disease associations (from GenCC):

• primary dysautonomia

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• Riley-Day syndrome

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 9-108901513-C-T is Benign according to our data. Variant chr9-108901513-C-T is described in ClinVar as Benign. ClinVar VariationId is 137575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.14 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5	c.1926G>A	p.Thr642Thr	synonymous_variant	Exon 18 of 37	ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2	c.1584G>A	p.Thr528Thr	synonymous_variant	Exon 18 of 37		NP_001305289.1
ELP1	NM_001330749.2	c.879G>A	p.Thr293Thr	synonymous_variant	Exon 16 of 35		NP_001317678.1
ELP1	XM_047423991.1	c.1926G>A	p.Thr642Thr	synonymous_variant	Exon 18 of 25		XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10	c.1926G>A	p.Thr642Thr	synonymous_variant	Exon 18 of 37	1	NM_003640.5	ENSP00000363779.5

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14189 AN: 152022 Hom.: 860 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0612

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0510

Gnomad FIN AF: 0.0975

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0808

Gnomad OTH AF: 0.0823

GnomAD2 exomes AF: 0.0715 AC: 17953 AN: 251124 AF XY: 0.0714

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0424

Gnomad ASJ exome AF: 0.0285

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.0925

Gnomad NFE exome AF: 0.0849

Gnomad OTH exome AF: 0.0694

GnomAD4 exome AF: 0.0769 AC: 112226 AN: 1458744 Hom.: 4889 Cov.: 32 AF XY: 0.0760 AC XY: 55200 AN XY: 725844

African (AFR) AF: 0.148 AC: 4929 AN: 33328

American (AMR) AF: 0.0447 AC: 1997 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0292 AC: 763 AN: 26130

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39692

South Asian (SAS) AF: 0.0537 AC: 4633 AN: 86202

European-Finnish (FIN) AF: 0.0888 AC: 4743 AN: 53414

Middle Eastern (MID) AF: 0.0451 AC: 260 AN: 5768

European-Non Finnish (NFE) AF: 0.0817 AC: 90626 AN: 1109182

Other (OTH) AF: 0.0707 AC: 4265 AN: 60308

GnomAD4 genome AF: 0.0933 AC: 14201 AN: 152140 Hom.: 856 Cov.: 31 AF XY: 0.0924 AC XY: 6873 AN XY: 74360

African (AFR) AF: 0.149 AC: 6188 AN: 41488

American (AMR) AF: 0.0610 AC: 931 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.0508 AC: 245 AN: 4822

European-Finnish (FIN) AF: 0.0975 AC: 1031 AN: 10574

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0808 AC: 5496 AN: 68006

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.0871 Hom.: 1433

Bravo AF: 0.0945

Asia WGS AF: 0.0300 AC: 103 AN: 3478

EpiCase AF: 0.0791

EpiControl AF: 0.0749

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial dysautonomia Benign:3

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

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 07, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.95
DANN	Benign	0.49
PhyloP100		-3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10979605; hg19: chr9-111663793;