Variant rs2275630 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.856

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
ELP1	NM_003640.5 linkuse as main transcript	c.2130+133T>C	intron_variant	ENST00000374647.10
ELP1	NM_001318360.2 linkuse as main transcript	c.1788+133T>C	intron_variant
ELP1	NM_001330749.2 linkuse as main transcript	c.1083+133T>C	intron_variant
ELP1	XM_047423991.1 linkuse as main transcript	c.2130+133T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP1	ENST00000374647.10 linkuse as main transcript	c.2130+133T>C		intron_variant		1	NM_003640.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0229

AC:

3492

AN:

152212

Hom.:

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.0615

Gnomad4 AMR exome

AF:

0.00636

Gnomad4 ASJ exome

AF:

0.00356

Gnomad4 EAS exome

AF:

0.112

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.00274

Gnomad4 NFE exome

AF:

0.00385

Gnomad4 OTH exome

AF:

0.0161

GnomAD4 genome

AF:

0.0230

AC:

3498

AN:

152330

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1691

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0593

Gnomad4 AMR

AF:

0.00791

Gnomad4 ASJ

AF:

0.00374

Gnomad4 EAS

AF:

0.0983

Gnomad4 SAS

AF:

0.0128

Gnomad4 FIN

AF:

0.00348

Gnomad4 NFE

AF:

0.00357

Gnomad4 OTH

AF:

0.0198

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.0260

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.1

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over