rs398102543

Variant names:

• chr9-108917684-C-CA
• rs398102543
• NM_003640.5:c.741-15dupT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003640.5(ELP1):​c.741-15dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,613,212 control chromosomes in the GnomAD database, including 10,928 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1180 hom., cov: 30)
  • Exomes 𝑓: 0.11 (9748 hom.)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.297
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 9-108917684-C-CA is Benign according to our data. Variant chr9-108917684-C-CA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5	c.741-15dupT		intron_variant	Intron 8 of 36	ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2	c.399-15dupT		intron_variant	Intron 8 of 36		NP_001305289.1
ELP1	NM_001330749.2	c.-307-15dupT		intron_variant	Intron 6 of 34		NP_001317678.1
ELP1	XM_047423991.1	c.741-15dupT		intron_variant	Intron 8 of 24		XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10	c.741-15dupT		intron_variant	Intron 8 of 36	1	NM_003640.5	ENSP00000363779.5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17314 AN: 152030 Hom.: 1180 Cov.: 30

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0840

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0407

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.0943 AC: 23705 AN: 251456 AF XY: 0.0936

Gnomad AFR exome AF: 0.146

Gnomad AMR exome AF: 0.0551

Gnomad ASJ exome AF: 0.0981

Gnomad EAS exome AF: 0.000870

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.120

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.110 AC: 161361 AN: 1461064 Hom.: 9748 Cov.: 33 AF XY: 0.109 AC XY: 78887 AN XY: 726892

African (AFR) AF: 0.146 AC: 4901 AN: 33470

American (AMR) AF: 0.0581 AC: 2598 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2653 AN: 26130

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39678

South Asian (SAS) AF: 0.0470 AC: 4056 AN: 86246

European-Finnish (FIN) AF: 0.126 AC: 6741 AN: 53408

Middle Eastern (MID) AF: 0.137 AC: 791 AN: 5764

European-Non Finnish (NFE) AF: 0.120 AC: 133174 AN: 1111284

Other (OTH) AF: 0.106 AC: 6428 AN: 60362

GnomAD4 genome AF: 0.114 AC: 17325 AN: 152148 Hom.: 1180 Cov.: 30 AF XY: 0.111 AC XY: 8248 AN XY: 74374

African (AFR) AF: 0.144 AC: 5984 AN: 41482

American (AMR) AF: 0.0838 AC: 1281 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5190

South Asian (SAS) AF: 0.0411 AC: 198 AN: 4814

European-Finnish (FIN) AF: 0.129 AC: 1362 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7745 AN: 68006

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.107 Hom.: 205

Bravo AF: 0.113

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial dysautonomia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs398102543; hg19: chr9-111679964;