rs746116617

Variant names:

• chr9-108908323-TGAG-T
• rs746116617
• NM_003640.5:c.1439_1441delCTC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_003640.5(ELP1):​c.1439_1441delCTC​(p.Pro480del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000163 in 1,613,602 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: ELP1 NM_003640.5 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:6
• Conservation: PhyloP100: 4.07
• Publications: 0 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: Orphanet, G2P
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_003640.5. Strenght limited to Supporting due to length of the change: 1aa.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP1	NM_003640.5	MANE Select	c.1439_1441delCTC	p.Pro480del	disruptive_inframe_deletion	Exon 13 of 37	NP_003631.2
	ELP1	NM_001318360.2		c.1097_1099delCTC	p.Pro366del	disruptive_inframe_deletion	Exon 13 of 37	NP_001305289.1	A0A6Q8PGW3
	ELP1	NM_001330749.2		c.392_394delCTC	p.Pro131del	disruptive_inframe_deletion	Exon 11 of 35	NP_001317678.1	F5H2T0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP1	ENST00000374647.10	TSL:1 MANE Select	c.1439_1441delCTC	p.Pro480del	disruptive_inframe_deletion	Exon 13 of 37	ENSP00000363779.5	O95163
	ELP1	ENST00000537196.1	TSL:1	c.392_394delCTC	p.Pro131del	disruptive_inframe_deletion	Exon 6 of 30	ENSP00000439367.1	F5H2T0
	ELP1	ENST00000495759.6	TSL:1	n.*49_*51delCTC		non_coding_transcript_exon	Exon 7 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000107 AC: 27 AN: 251340 AF XY: 0.000110

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000164 AC: 240 AN: 1461272 Hom.: 0 AF XY: 0.000193 AC XY: 140 AN XY: 727018

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000211 AC: 234 AN: 1111442

Other (OTH) AF: 0.0000662 AC: 4 AN: 60380

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13 AN XY: 74484

African (AFR) AF: 0.0000481 AC: 2 AN: 41582

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000162 Hom.: 0

Bravo AF: 0.000144

EpiCase AF: 0.000218

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Familial dysautonomia (2)
-	2	-	not provided (2)
-	1	-	Familial dysautonomia;C0025149:Medulloblastoma (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs746116617; hg19: chr9-111670603;