chr9-108889742-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003640.5(ELP1):​c.3161-349G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 356,194 control chromosomes in the GnomAD database, including 7,881 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.22 ( 4012 hom., cov: 32)
Exomes 𝑓: 0.19 ( 3869 hom. )

Consequence

ELP1
NM_003640.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0440
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ELP1NM_003640.5 linkuse as main transcriptc.3161-349G>T intron_variant ENST00000374647.10 NP_003631.2
ELP1NM_001318360.2 linkuse as main transcriptc.2819-349G>T intron_variant NP_001305289.1
ELP1NM_001330749.2 linkuse as main transcriptc.2114-349G>T intron_variant NP_001317678.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ELP1ENST00000374647.10 linkuse as main transcriptc.3161-349G>T intron_variant 1 NM_003640.5 ENSP00000363779 P1

Frequencies

GnomAD3 genomes
AF:
0.218
AC:
33040
AN:
151906
Hom.:
4009
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.319
Gnomad AMI
AF:
0.273
Gnomad AMR
AF:
0.160
Gnomad ASJ
AF:
0.225
Gnomad EAS
AF:
0.293
Gnomad SAS
AF:
0.229
Gnomad FIN
AF:
0.185
Gnomad MID
AF:
0.201
Gnomad NFE
AF:
0.167
Gnomad OTH
AF:
0.199
GnomAD4 exome
AF:
0.189
AC:
38678
AN:
204170
Hom.:
3869
AF XY:
0.193
AC XY:
21198
AN XY:
110102
show subpopulations
Gnomad4 AFR exome
AF:
0.329
Gnomad4 AMR exome
AF:
0.157
Gnomad4 ASJ exome
AF:
0.226
Gnomad4 EAS exome
AF:
0.293
Gnomad4 SAS exome
AF:
0.219
Gnomad4 FIN exome
AF:
0.188
Gnomad4 NFE exome
AF:
0.166
Gnomad4 OTH exome
AF:
0.191
GnomAD4 genome
AF:
0.217
AC:
33063
AN:
152024
Hom.:
4012
Cov.:
32
AF XY:
0.218
AC XY:
16210
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.319
Gnomad4 AMR
AF:
0.160
Gnomad4 ASJ
AF:
0.225
Gnomad4 EAS
AF:
0.292
Gnomad4 SAS
AF:
0.229
Gnomad4 FIN
AF:
0.185
Gnomad4 NFE
AF:
0.167
Gnomad4 OTH
AF:
0.198
Alfa
AF:
0.205
Hom.:
567
Bravo
AF:
0.220
Asia WGS
AF:
0.274
AC:
953
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
4.5
DANN
Benign
0.80

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: rs10118853; hg19: chr9-111652022; API