rs4369056

Positions:

• chr9-108906158-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003640.5(ELP1):​c.1643+145G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 764,234 control chromosomes in the GnomAD database, including 11,443 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3466 hom., cov: 32)
  • Exomes 𝑓: 0.15 (7977 hom.)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.702

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-108906158-C-T is Benign according to our data. Variant chr9-108906158-C-T is described in ClinVar as [Benign]. Clinvar id is 1229125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP1	NM_003640.5	c.1643+145G>A		intron_variant		ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2	c.1301+145G>A		intron_variant			NP_001305289.1
ELP1	NM_001330749.2	c.596+145G>A		intron_variant			NP_001317678.1
ELP1	XM_047423991.1	c.1643+145G>A		intron_variant			XP_047279947.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10	c.1643+145G>A		intron_variant		1	NM_003640.5	ENSP00000363779.5

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29583 AN: 151956 Hom.: 3456 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.283

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.0626

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.172

GnomAD4 exome AF: 0.150 AC: 91775 AN: 612158 Hom.: 7977 AF XY: 0.149 AC XY: 48188 AN XY: 324410

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.234

Gnomad4 ASJ exome AF: 0.0696

Gnomad4 EAS exome AF: 0.288

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.160

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.195 AC: 29629 AN: 152076 Hom.: 3466 Cov.: 32 AF XY: 0.197 AC XY: 14633 AN XY: 74318

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0626

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.170

Alfa AF: 0.150 Hom.: 685

Bravo AF: 0.207

Asia WGS AF: 0.255 AC: 888 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.52

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: rs4369056; hg19: chr9-111668438; COSMIC: COSV65898078;