rs2230788

Variant names:

• chr9-108926548-C-T
• rs2230788
• NM_003640.5:c.441G>A
• ELP1 p.Gln147Gln

Your query was ambiguous. Multiple possible variants found:

• chr9-108926548-C-T
• chr9-108926548-C-G

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.441G>A​(p.Gln147Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,611,970 control chromosomes in the GnomAD database, including 6,925 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (585 hom., cov: 32)
  • Exomes 𝑓: 0.091 (6340 hom.)
• Consequence: ELP1 NM_003640.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.05
• Publications: 16 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=-0.57).
• BP6: Variant 9-108926548-C-T is Benign according to our data. Variant chr9-108926548-C-T is described in ClinVar as Benign. ClinVar VariationId is 137583.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 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.441G>A	p.Gln147Gln	synonymous	Exon 5 of 37	NP_003631.2
	ELP1	NM_001318360.2		c.99G>A	p.Gln33Gln	synonymous	Exon 5 of 37	NP_001305289.1	A0A6Q8PGW3
	ELP1	NM_001330749.2		c.-419G>A		5_prime_UTR	Exon 5 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.441G>A	p.Gln147Gln	synonymous	Exon 5 of 37	ENSP00000363779.5	O95163
	ELP1	ENST00000537196.1	TSL:1	c.-308+7316G>A		intron	N/A	ENSP00000439367.1	F5H2T0
	ELP1	ENST00000495759.6	TSL:1	n.441G>A		non_coding_transcript_exon	Exon 5 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12367 AN: 152112 Hom.: 585 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.0908

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0911

Gnomad OTH AF: 0.0969

GnomAD2 exomes AF: 0.0944 AC: 23659 AN: 250620 AF XY: 0.0956

Gnomad AFR exome AF: 0.0385

Gnomad AMR exome AF: 0.0909

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.110

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.0893

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0911 AC: 132925 AN: 1459740 Hom.: 6340 Cov.: 31 AF XY: 0.0919 AC XY: 66765 AN XY: 726190

African (AFR) AF: 0.0425 AC: 1421 AN: 33460

American (AMR) AF: 0.0922 AC: 4119 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3944 AN: 26104

East Asian (EAS) AF: 0.145 AC: 5766 AN: 39676

South Asian (SAS) AF: 0.0970 AC: 8366 AN: 86214

European-Finnish (FIN) AF: 0.116 AC: 6103 AN: 52646

Middle Eastern (MID) AF: 0.110 AC: 636 AN: 5766

European-Non Finnish (NFE) AF: 0.0871 AC: 96779 AN: 1110844

Other (OTH) AF: 0.0960 AC: 5791 AN: 60346

GnomAD4 genome AF: 0.0812 AC: 12365 AN: 152230 Hom.: 585 Cov.: 32 AF XY: 0.0827 AC XY: 6157 AN XY: 74438

African (AFR) AF: 0.0425 AC: 1766 AN: 41552

American (AMR) AF: 0.0856 AC: 1309 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3470

East Asian (EAS) AF: 0.115 AC: 596 AN: 5172

South Asian (SAS) AF: 0.0913 AC: 441 AN: 4832

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10576

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 292

European-Non Finnish (NFE) AF: 0.0911 AC: 6196 AN: 68010

Other (OTH) AF: 0.0955 AC: 202 AN: 2116

Alfa AF: 0.0829 Hom.: 405

Bravo AF: 0.0768

Asia WGS AF: 0.119 AC: 414 AN: 3478

EpiCase AF: 0.0922

EpiControl AF: 0.0857

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Familial dysautonomia (3)
-	-	3	not specified (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.9
DANN	Benign	0.41
PhyloP100		-1.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2230788;

hg19: chr9-111688828;

COSMIC: COSV65899026;