rs10118853

Positions:

• chr9-108889742-C-A
• chr9-108889742-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003640.5(ELP1):​c.3161-349G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 356,194 control chromosomes in the GnomAD database, including 7,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4012 hom., cov: 32)
  • Exomes 𝑓: 0.19 (3869 hom.)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0440

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP1	NM_003640.5	c.3161-349G>T		intron_variant		ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2	c.2819-349G>T		intron_variant			NP_001305289.1
ELP1	NM_001330749.2	c.2114-349G>T		intron_variant			NP_001317678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10	c.3161-349G>T		intron_variant		1	NM_003640.5	ENSP00000363779	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33040 AN: 151906 Hom.: 4009 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.199

GnomAD4 exome AF: 0.189 AC: 38678 AN: 204170 Hom.: 3869 AF XY: 0.193 AC XY: 21198 AN XY: 110102

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.166

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.217 AC: 33063 AN: 152024 Hom.: 4012 Cov.: 32 AF XY: 0.218 AC XY: 16210 AN XY: 74314

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.292

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.198

Alfa AF: 0.205 Hom.: 567

Bravo AF: 0.220

Asia WGS AF: 0.274 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.5
DANN	Benign	0.80

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: rs10118853; hg19: chr9-111652022;