chr9-108867856-G-C

Variant summary

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

The NM_003640.5(ELP1):​c.*1259C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 152,236 control chromosomes in the GnomAD database, including 669 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 669 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ELP1
NM_003640.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0640
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]

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=-0.89).
BP6
Variant 9-108867856-G-C is Benign according to our data. Variant chr9-108867856-G-C is described in ClinVar as [Benign]. Clinvar id is 364539.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ELP1NM_003640.5 linkuse as main transcriptc.*1259C>G 3_prime_UTR_variant 37/37 ENST00000374647.10
ELP1NM_001318360.2 linkuse as main transcriptc.*1259C>G 3_prime_UTR_variant 37/37
ELP1NM_001330749.2 linkuse as main transcriptc.*1259C>G 3_prime_UTR_variant 35/35

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ELP1ENST00000374647.10 linkuse as main transcriptc.*1259C>G 3_prime_UTR_variant 37/371 NM_003640.5 P1

Frequencies

GnomAD3 genomes
AF:
0.0809
AC:
12307
AN:
152118
Hom.:
668
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0561
Gnomad AMI
AF:
0.0241
Gnomad AMR
AF:
0.0884
Gnomad ASJ
AF:
0.0927
Gnomad EAS
AF:
0.142
Gnomad SAS
AF:
0.294
Gnomad FIN
AF:
0.0585
Gnomad MID
AF:
0.123
Gnomad NFE
AF:
0.0781
Gnomad OTH
AF:
0.0790
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
2
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2
Gnomad4 NFE exome
AF:
0.00
GnomAD4 genome
AF:
0.0810
AC:
12337
AN:
152236
Hom.:
669
Cov.:
33
AF XY:
0.0845
AC XY:
6292
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.0564
Gnomad4 AMR
AF:
0.0889
Gnomad4 ASJ
AF:
0.0927
Gnomad4 EAS
AF:
0.142
Gnomad4 SAS
AF:
0.295
Gnomad4 FIN
AF:
0.0585
Gnomad4 NFE
AF:
0.0781
Gnomad4 OTH
AF:
0.0796
Alfa
AF:
0.0732
Hom.:
73
Bravo
AF:
0.0762
Asia WGS
AF:
0.204
AC:
708
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Familial dysautonomia Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.55
DANN
Benign
0.66

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.

Other links and lift over

dbSNP: rs13299652; hg19: chr9-111630136; API