9-108867764-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003640.5(ELP1):c.*1351C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,074 control chromosomes in the GnomAD database, including 15,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (15237 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ELP1 NM_003640.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.00

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 9-108867764-G-T is Benign according to our data. Variant chr9-108867764-G-T is described in ClinVar as [Benign]. Clinvar id is 364536.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.683 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP1	NM_003640.5	c.*1351C>A		3_prime_UTR_variant	37/37	ENST00000374647.10
ELP1	NM_001318360.2	c.*1351C>A		3_prime_UTR_variant	37/37
ELP1	NM_001330749.2	c.*1351C>A		3_prime_UTR_variant	35/35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP1	ENST00000374647.10	c.*1351C>A		3_prime_UTR_variant	37/37	1	NM_003640.5	P1

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62277 AN: 151956 Hom.: 15221 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.366

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.410 AC: 62329 AN: 152074 Hom.: 15237 Cov.: 33 AF XY: 0.410 AC XY: 30512 AN XY: 74332

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.362

Alfa AF: 0.345 Hom.: 2513

Bravo AF: 0.427

Asia WGS AF: 0.394 AC: 1370 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial dysautonomia Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.7
Dann	Benign	0.24

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

Other links and lift over

dbSNP: rs4978371; hg19: chr9-111630044;