rs10979596

chr9-108894723-T-G

Variant summary

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

The NM_003640.5(ELP1):c.2737-657A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 152,272 control chromosomes in the GnomAD database, including 649 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 0.086 (649 hom., cov: 32)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP1	NM_003640.5	c.2737-657A>C		intron_variant		ENST00000374647.10
ELP1	NM_001318360.2	c.2395-657A>C		intron_variant
ELP1	NM_001330749.2	c.1690-657A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP1	ENST00000374647.10	c.2737-657A>C		intron_variant		1	NM_003640.5	P1

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13062 AN: 152156 Hom.: 646 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0650

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0741

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0859 AC: 13082 AN: 152272 Hom.: 649 Cov.: 32 AF XY: 0.0860 AC XY: 6405 AN XY: 74458

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.0580

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0650

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0818 Hom.: 78

Bravo AF: 0.0860

Asia WGS AF: 0.145 AC: 505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	5.5
Dann	Benign	0.87

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: rs10979596; hg19: chr9-111657003;