9-108905545-A-G

Variant names:

• chr9-108905545-A-G
• rs10979607
• NM_003640.5:c.1643+758T>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.1643+758T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 152,272 control chromosomes in the GnomAD database, including 573 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 0.080 (573 hom., cov: 32)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.154 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003640.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP1	NM_003640.5	MANE Select	c.1643+758T>C		intron	N/A	NP_003631.2
	ELP1	NM_001318360.2		c.1301+758T>C		intron	N/A	NP_001305289.1
	ELP1	NM_001330749.2		c.596+758T>C		intron	N/A	NP_001317678.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP1	ENST00000374647.10	TSL:1 MANE Select	c.1643+758T>C		intron	N/A	ENSP00000363779.5
	ELP1	ENST00000537196.1	TSL:1	c.596+758T>C		intron	N/A	ENSP00000439367.1
	ELP1	ENST00000495759.6	TSL:1	n.*253+758T>C		intron	N/A	ENSP00000433514.2

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12191 AN: 152154 Hom.: 570 Cov.: 32

Gnomad AFR AF: 0.0828

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0752

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0802 AC: 12211 AN: 152272 Hom.: 573 Cov.: 32 AF XY: 0.0808 AC XY: 6019 AN XY: 74472

African (AFR) AF: 0.0832 AC: 3459 AN: 41560

American (AMR) AF: 0.0560 AC: 856 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0452 AC: 157 AN: 3472

East Asian (EAS) AF: 0.163 AC: 845 AN: 5184

South Asian (SAS) AF: 0.145 AC: 698 AN: 4826

European-Finnish (FIN) AF: 0.0649 AC: 689 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0752 AC: 5110 AN: 67994

Other (OTH) AF: 0.0714 AC: 151 AN: 2114

Alfa AF: 0.0793 Hom.: 76

Bravo AF: 0.0795

Asia WGS AF: 0.147 AC: 511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.40
PhyloP100		-0.080
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: rs10979607; hg19: chr9-111667825;