rs10979596

Variant names:

• chr9-108894723-T-G
• rs10979596
• NM_003640.5:c.2737-657A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 -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 rank	MANE	Protein	UniProt
ELP1	NM_003640.5	c.2737-657A>C		intron_variant	Intron 25 of 36	ENST00000374647.10	NP_003631.2
ELP1	NM_001318360.2	c.2395-657A>C		intron_variant	Intron 25 of 36		NP_001305289.1
ELP1	NM_001330749.2	c.1690-657A>C		intron_variant	Intron 23 of 34		NP_001317678.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10	c.2737-657A>C		intron_variant	Intron 25 of 36	1	NM_003640.5	ENSP00000363779.5

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

African (AFR) AF: 0.107 AC: 4453 AN: 41540

American (AMR) AF: 0.0580 AC: 887 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3472

East Asian (EAS) AF: 0.160 AC: 827 AN: 5184

South Asian (SAS) AF: 0.138 AC: 664 AN: 4822

European-Finnish (FIN) AF: 0.0650 AC: 690 AN: 10612

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0740 AC: 5037 AN: 68022

Other (OTH) AF: 0.0743 AC: 157 AN: 2114

Alfa AF: 0.0820 Hom.: 81

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

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

Other links and lift over

dbSNP: rs10979596; hg19: chr9-111657003;