9-108891294-C-G

Variant names:

• chr9-108891294-C-G
• rs1063110
• NM_003640.5:c.3069G>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003640.5(ELP1):​c.3069G>C​(p.Leu1023Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 1,613,932 control chromosomes in the GnomAD database, including 151,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L1023L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.35 (10889 hom., cov: 33)
  • Exomes 𝑓: 0.43 (140588 hom.)
• Consequence: ELP1 NM_003640.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 1.25
• Publications: 20 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 9-108891294-C-G is Benign according to our data. Variant chr9-108891294-C-G is described in ClinVar as Benign. ClinVar VariationId is 259111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 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.3069G>C	p.Leu1023Leu	synonymous	Exon 28 of 37	NP_003631.2
	ELP1	NM_001318360.2		c.2727G>C	p.Leu909Leu	synonymous	Exon 28 of 37	NP_001305289.1	A0A6Q8PGW3
	ELP1	NM_001330749.2		c.2022G>C	p.Leu674Leu	synonymous	Exon 26 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.3069G>C	p.Leu1023Leu	synonymous	Exon 28 of 37	ENSP00000363779.5	O95163
	ELP1	ENST00000537196.1	TSL:1	c.2022G>C	p.Leu674Leu	synonymous	Exon 21 of 30	ENSP00000439367.1	F5H2T0
	ELP1	ENST00000495759.6	TSL:1	n.*1679G>C		non_coding_transcript_exon	Exon 22 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52791 AN: 152014 Hom.: 10883 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.396

GnomAD2 exomes AF: 0.402 AC: 100781 AN: 250962 AF XY: 0.403

Gnomad AFR exome AF: 0.0943

Gnomad AMR exome AF: 0.418

Gnomad ASJ exome AF: 0.492

Gnomad EAS exome AF: 0.452

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.426

GnomAD4 exome AF: 0.433 AC: 633540 AN: 1461798 Hom.: 140588 Cov.: 55 AF XY: 0.431 AC XY: 313407 AN XY: 727200

African (AFR) AF: 0.0909 AC: 3043 AN: 33480

American (AMR) AF: 0.419 AC: 18750 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.490 AC: 12801 AN: 26136

East Asian (EAS) AF: 0.421 AC: 16694 AN: 39696

South Asian (SAS) AF: 0.318 AC: 27392 AN: 86254

European-Finnish (FIN) AF: 0.403 AC: 21528 AN: 53408

Middle Eastern (MID) AF: 0.449 AC: 2588 AN: 5766

European-Non Finnish (NFE) AF: 0.454 AC: 505040 AN: 1111946

Other (OTH) AF: 0.426 AC: 25704 AN: 60388

GnomAD4 genome AF: 0.347 AC: 52804 AN: 152134 Hom.: 10889 Cov.: 33 AF XY: 0.347 AC XY: 25765 AN XY: 74348

African (AFR) AF: 0.103 AC: 4287 AN: 41552

American (AMR) AF: 0.445 AC: 6802 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1688 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2312 AN: 5160

South Asian (SAS) AF: 0.300 AC: 1450 AN: 4826

European-Finnish (FIN) AF: 0.398 AC: 4204 AN: 10574

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30768 AN: 67970

Other (OTH) AF: 0.401 AC: 846 AN: 2108

Alfa AF: 0.338 Hom.: 1672

Bravo AF: 0.341

Asia WGS AF: 0.347 AC: 1207 AN: 3478

EpiCase AF: 0.447

EpiControl AF: 0.457

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Familial dysautonomia (4)
-	-	3	not provided (3)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	7.8
DANN	Benign	0.68
PhyloP100		1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
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: rs1063110; hg19: chr9-111653574; COSMIC: COSV65896937; COSMIC: COSV65896937;