chr9-108894752-T-A

Variant names:

• chr9-108894752-T-A
• rs10979597
• NM_003640.5:c.2737-686A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003640.5(ELP1):​c.2737-686A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 152,210 control chromosomes in the GnomAD database, including 643 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 (643 hom., cov: 32)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.15 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.2737-686A>T		intron	N/A	NP_003631.2
	ELP1	NM_001318360.2		c.2395-686A>T		intron	N/A	NP_001305289.1
	ELP1	NM_001330749.2		c.1690-686A>T		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.2737-686A>T		intron	N/A	ENSP00000363779.5
	ELP1	ENST00000537196.1	TSL:1	c.1690-686A>T		intron	N/A	ENSP00000439367.1
	ELP1	ENST00000495759.6	TSL:1	n.*1347-686A>T		intron	N/A	ENSP00000433514.2

Frequencies

GnomAD3 genomes AF: 0.0857 AC: 13039 AN: 152094 Hom.: 640 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: 0.159

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.0648

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.0740

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

GnomAD4 genome AF: 0.0858 AC: 13059 AN: 152210 Hom.: 643 Cov.: 32 AF XY: 0.0859 AC XY: 6391 AN XY: 74428

African (AFR) AF: 0.107 AC: 4440 AN: 41512

American (AMR) AF: 0.0579 AC: 886 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3470

East Asian (EAS) AF: 0.159 AC: 821 AN: 5166

South Asian (SAS) AF: 0.138 AC: 664 AN: 4816

European-Finnish (FIN) AF: 0.0648 AC: 688 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0740 AC: 5036 AN: 68016

Other (OTH) AF: 0.0742 AC: 157 AN: 2116

Alfa AF: 0.0858 Hom.: 64

Bravo AF: 0.0861

Asia WGS AF: 0.145 AC: 503 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.40
DANN	Benign	0.75
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs10979597; hg19: chr9-111657032;