rs751179612

Variant names:

• chr9-108894025-T-C
• rs751179612
• NM_003640.5:c.2778A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_003640.5(ELP1):​c.2778A>G​(p.Lys926Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00004 in 1,575,750 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: ELP1 NM_003640.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.51
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 9-108894025-T-C is Benign according to our data. Variant chr9-108894025-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 526205.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.51 with no splicing effect.

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.2778A>G	p.Lys926Lys	synonymous	Exon 26 of 37	NP_003631.2
	ELP1	NM_001318360.2		c.2436A>G	p.Lys812Lys	synonymous	Exon 26 of 37	NP_001305289.1	A0A6Q8PGW3
	ELP1	NM_001330749.2		c.1731A>G	p.Lys577Lys	synonymous	Exon 24 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.2778A>G	p.Lys926Lys	synonymous	Exon 26 of 37	ENSP00000363779.5	O95163
	ELP1	ENST00000537196.1	TSL:1	c.1731A>G	p.Lys577Lys	synonymous	Exon 19 of 30	ENSP00000439367.1	F5H2T0
	ELP1	ENST00000495759.6	TSL:1	n.*1388A>G		non_coding_transcript_exon	Exon 20 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000160 AC: 4 AN: 250454 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

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: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000429 AC: 61 AN: 1423560 Hom.: 0 Cov.: 26 AF XY: 0.0000422 AC XY: 30 AN XY: 710598

African (AFR) AF: 0.00 AC: 0 AN: 32708

American (AMR) AF: 0.00 AC: 0 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39466

South Asian (SAS) AF: 0.00 AC: 0 AN: 85352

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.0000510 AC: 55 AN: 1077640

Other (OTH) AF: 0.000102 AC: 6 AN: 59088

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152190 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

African (AFR) AF: 0.00 AC: 0 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.0000189

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	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
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.9
DANN	Benign	0.69
PhyloP100		1.5

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: rs751179612; hg19: chr9-111656305;