9-108929883-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_003640.5(ELP1):c.189C>G(p.Leu63Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,750 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 (★). Synonymous variant affecting the same amino acid position (i.e. L63L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ELP1
NM_003640.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0500

Publications

7 publications found

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 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: G2P, Orphanet
medulloblastoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ELP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 9-108929883-G-C is Benign according to our data. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-108929883-G-C is described in CliVar as Likely_benign. Clinvar id is 1144410.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.05 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP1	NM_003640.5 link	c.189C>G	p.Leu63Leu	synonymous_variant	Exon 3 of 37	ENST00000374647.10	NP_003631.2	O95163Q4LE38Q8N516

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP1	ENST00000374647.10 link	c.189C>G	p.Leu63Leu	synonymous_variant	Exon 3 of 37	1	NM_003640.5	ENSP00000363779.5		O95163

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461576

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5540

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111992

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 20, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

5.5

(source)

DANN

Benign

0.78

PhyloP100

0.050

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over