rs79596285

Variant names:

• chr9-108879526-G-A
• rs79596285
• NM_003640.5:c.3492C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003640.5(ELP1):​c.3492C>T​(p.Asp1164Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,613,992 control chromosomes in the GnomAD database, including 1,011 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (114 hom., cov: 33)
  • Exomes 𝑓: 0.0086 (897 hom.)
• Consequence: ELP1 NM_003640.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.121
• 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: Orphanet, G2P
• medulloblastoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 9-108879526-G-A is Benign according to our data. Variant chr9-108879526-G-A is described in ClinVar as Benign. ClinVar VariationId is 364557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.121 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0853 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP1	NM_003640.5	MANE Select	c.3492C>T	p.Asp1164Asp	synonymous	Exon 33 of 37	NP_003631.2
	ELP1	NM_001318360.2		c.3150C>T	p.Asp1050Asp	synonymous	Exon 33 of 37	NP_001305289.1	A0A6Q8PGW3
	ELP1	NM_001330749.2		c.2445C>T	p.Asp815Asp	synonymous	Exon 31 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.3492C>T	p.Asp1164Asp	synonymous	Exon 33 of 37	ENSP00000363779.5	O95163
	ELP1	ENST00000537196.1	TSL:1	c.2445C>T	p.Asp815Asp	synonymous	Exon 26 of 30	ENSP00000439367.1	F5H2T0
	ELP1	ENST00000495759.6	TSL:1	n.*2102C>T		non_coding_transcript_exon	Exon 27 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2304 AN: 152140 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.00319

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0885

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.0447

Gnomad SAS AF: 0.00437

Gnomad FIN AF: 0.0416

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.0143

GnomAD2 exomes AF: 0.0331 AC: 8326 AN: 251308 AF XY: 0.0267

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.00209

Gnomad EAS exome AF: 0.0446

Gnomad FIN exome AF: 0.0404

Gnomad NFE exome AF: 0.00131

Gnomad OTH exome AF: 0.0223

GnomAD4 exome AF: 0.00864 AC: 12636 AN: 1461734 Hom.: 897 Cov.: 31 AF XY: 0.00773 AC XY: 5623 AN XY: 727186

African (AFR) AF: 0.00209 AC: 70 AN: 33478

American (AMR) AF: 0.169 AC: 7550 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26134

East Asian (EAS) AF: 0.0464 AC: 1841 AN: 39692

South Asian (SAS) AF: 0.00212 AC: 183 AN: 86258

European-Finnish (FIN) AF: 0.0364 AC: 1942 AN: 53418

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.000456 AC: 507 AN: 1111874

Other (OTH) AF: 0.00815 AC: 492 AN: 60394

GnomAD4 genome AF: 0.0152 AC: 2317 AN: 152258 Hom.: 114 Cov.: 33 AF XY: 0.0179 AC XY: 1336 AN XY: 74432

African (AFR) AF: 0.00318 AC: 132 AN: 41558

American (AMR) AF: 0.0892 AC: 1365 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.0448 AC: 232 AN: 5174

South Asian (SAS) AF: 0.00458 AC: 22 AN: 4806

European-Finnish (FIN) AF: 0.0416 AC: 441 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00138 AC: 94 AN: 68022

Other (OTH) AF: 0.0137 AC: 29 AN: 2116

Alfa AF: 0.00645 Hom.: 43

Bravo AF: 0.0218

Asia WGS AF: 0.0290 AC: 101 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.00113

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	2	Familial dysautonomia (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.5
DANN	Benign	0.58
PhyloP100		0.12
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: rs79596285; hg19: chr9-111641806; COSMIC: COSV65896761;