rs2230798

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003640.5(ELP1):c.2855A>T(p.Lys952Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0178 in 1,613,514 control chromosomes in the GnomAD database, including 365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K952Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.014 ( 15 hom., cov: 32)

Exomes 𝑓: 0.018 ( 350 hom. )

Consequence

ELP1
NM_003640.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 3.51

Publications

17 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: Orphanet, G2P
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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010479808).

BP6

Variant 9-108893948-T-A is Benign according to our data. Variant chr9-108893948-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0525 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELP1	NM_003640.5	MANE Select	c.2855A>T	p.Lys952Ile	missense	Exon 26 of 37	NP_003631.2
ELP1	NM_001318360.2		c.2513A>T	p.Lys838Ile	missense	Exon 26 of 37	NP_001305289.1	A0A6Q8PGW3
ELP1	NM_001330749.2		c.1808A>T	p.Lys603Ile	missense	Exon 24 of 35	NP_001317678.1	F5H2T0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ELP1	ENST00000374647.10	TSL:1 MANE Select	c.2855A>T	p.Lys952Ile	missense	Exon 26 of 37	ENSP00000363779.5	O95163
ELP1	ENST00000537196.1	TSL:1	c.1808A>T	p.Lys603Ile	missense	Exon 19 of 30	ENSP00000439367.1	F5H2T0
ELP1	ENST00000495759.6	TSL:1	n.*1465A>T		non_coding_transcript_exon	Exon 20 of 31	ENSP00000433514.2	H0YDF3

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2075

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00348

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.0328

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0255

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0115

GnomAD2 exomes

AF:

0.0157

AC:

3954

AN:

251192

AF XY:

0.0152

show subpopulations

Gnomad AFR exome

AF:

0.00289

Gnomad AMR exome

AF:

0.0153

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.0290

Gnomad FIN exome

AF:

0.0274

Gnomad NFE exome

AF:

0.0176

Gnomad OTH exome

AF:

0.0152

GnomAD4 exome

AF:

0.0182

AC:

26614

AN:

1461234

Hom.:

350

Cov.:

AF XY:

0.0177

AC XY:

12874

AN XY:

726932

show subpopulations

African (AFR)

AF:

0.00296

AC:

AN:

33464

American (AMR)

AF:

0.0167

AC:

745

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00245

AC:

AN:

26126

East Asian (EAS)

AF:

0.0544

AC:

2158

AN:

39640

South Asian (SAS)

AF:

0.00510

AC:

440

AN:

86242

European-Finnish (FIN)

AF:

0.0268

AC:

1427

AN:

53342

Middle Eastern (MID)

AF:

0.00330

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0187

AC:

20744

AN:

1111576

Other (OTH)

AF:

0.0152

AC:

918

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

1146

2291

3437

4582

5728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.0136

AC:

2072

AN:

152280

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1004

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00347

AC:

144

AN:

41558

American (AMR)

AF:

0.0120

AC:

183

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.0323

AC:

167

AN:

5178

South Asian (SAS)

AF:

0.00414

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0255

AC:

271

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0180

AC:

1226

AN:

68018

Other (OTH)

AF:

0.0114

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

102

203

305

406

508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0147

Hom.:

Bravo

AF:

0.0126

TwinsUK

AF:

0.0224

AC:

ALSPAC

AF:

0.0192

AC:

ESP6500AA

AF:

0.00431

AC:

ESP6500EA

AF:

0.0160

AC:

138

ExAC

AF:

0.0160

AC:

1946

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.0174

EpiControl

AF:

0.0164

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Familial dysautonomia (3)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.010

MetaSVM

Benign

-0.78

MutationAssessor

Pathogenic

3.2

PhyloP100

3.5

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-5.8

REVEL

Benign

0.16

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.44

MPC

0.54

ClinPred

0.082

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.58

gMVP

0.47

Mutation Taster

=89/11

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over