rs2275630

Variant names:

• chr9-108900127-A-G
• rs2275630
• NM_003640.5:c.2130+133T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003640.5(ELP1):​c.2130+133T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 818,312 control chromosomes in the GnomAD database, including 344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.023 (82 hom., cov: 32)
  • Exomes 𝑓: 0.012 (262 hom.)
• Consequence: ELP1 NM_003640.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.856
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 9-108900127-A-G is Benign according to our data. Variant chr9-108900127-A-G is described in ClinVar as Benign. ClinVar VariationId is 1237688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0912 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.2130+133T>C		intron	N/A	NP_003631.2
	ELP1	NM_001318360.2		c.1788+133T>C		intron	N/A	NP_001305289.1	A0A6Q8PGW3
	ELP1	NM_001330749.2		c.1083+133T>C		intron	N/A	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.2130+133T>C		intron	N/A	ENSP00000363779.5	O95163
	ELP1	ENST00000537196.1	TSL:1	c.1083+133T>C		intron	N/A	ENSP00000439367.1	F5H2T0
	ELP1	ENST00000495759.6	TSL:1	n.*740+133T>C		intron	N/A	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3492 AN: 152212 Hom.: 82 Cov.: 32

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0987

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00357

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0120 AC: 7980 AN: 665982 Hom.: 262 AF XY: 0.0116 AC XY: 4087 AN XY: 353618

African (AFR) AF: 0.0615 AC: 1061 AN: 17262

American (AMR) AF: 0.00636 AC: 218 AN: 34290

Ashkenazi Jewish (ASJ) AF: 0.00356 AC: 73 AN: 20488

East Asian (EAS) AF: 0.112 AC: 3643 AN: 32536

South Asian (SAS) AF: 0.0103 AC: 657 AN: 63884

European-Finnish (FIN) AF: 0.00274 AC: 127 AN: 46342

Middle Eastern (MID) AF: 0.0191 AC: 61 AN: 3190

European-Non Finnish (NFE) AF: 0.00385 AC: 1595 AN: 414140

Other (OTH) AF: 0.0161 AC: 545 AN: 33850

GnomAD4 genome AF: 0.0230 AC: 3498 AN: 152330 Hom.: 82 Cov.: 32 AF XY: 0.0227 AC XY: 1691 AN XY: 74494

African (AFR) AF: 0.0593 AC: 2464 AN: 41564

American (AMR) AF: 0.00791 AC: 121 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.0983 AC: 509 AN: 5178

South Asian (SAS) AF: 0.0128 AC: 62 AN: 4830

European-Finnish (FIN) AF: 0.00348 AC: 37 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00357 AC: 243 AN: 68038

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0136 Hom.: 18

Bravo AF: 0.0260

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		-0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs2275630; hg19: chr9-111662407; COSMIC: COSV65897980;