11-31539740-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_019040.5(ELP4):c.338T>C(p.Leu113Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0046 in 1,612,314 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 34 hom. )

Consequence

ELP4
NM_019040.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.34

Publications

7 publications found

Variant links:

Genes affected

ELP4 (HGNC:1171): (elongator acetyltransferase complex subunit 4) This gene encodes a component of the six subunit elongator complex, a histone acetyltransferase complex that associates directly with RNA polymerase II during transcriptional elongation. The human gene can partially complement sensitivity phenotypes of yeast ELP4 deletion mutants. This gene has also been associated with Rolandic epilepsy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ELP4 Gene-Disease associations (from GenCC):

aniridia 2
Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp
aniridia 1
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ELP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011266887).

BP6

Variant 11-31539740-T-C is Benign according to our data. Variant chr11-31539740-T-C is described in ClinVar as [Benign]. Clinvar id is 772330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 535 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5 link	c.338T>C	p.Leu113Ser	missense_variant	Exon 3 of 10	ENST00000640961.2	NP_061913.3	Q96EB1-1
ELP4	NM_001288726.2 link	c.338T>C	p.Leu113Ser	missense_variant	Exon 3 of 12		NP_001275655.1	Q96EB1G5E9D4
ELP4	NM_001288725.2 link	c.338T>C	p.Leu113Ser	missense_variant	Exon 3 of 11		NP_001275654.1	Q96EB1-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2 link	c.338T>C	p.Leu113Ser	missense_variant	Exon 3 of 10	1	NM_019040.5	ENSP00000492152.1		Q96EB1-1

Frequencies

GnomAD3 genomes

AF:

0.00351

AC:

535

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00514

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00476

AC:

1181

AN:

248216

AF XY:

0.00530

show subpopulations

Gnomad AFR exome

AF:

0.000647

Gnomad AMR exome

AF:

0.00212

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00144

Gnomad NFE exome

AF:

0.00477

Gnomad OTH exome

AF:

0.00367

GnomAD4 exome

AF:

0.00471

AC:

6876

AN:

1459980

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

3696

AN XY:

726192

show subpopulations

African (AFR)

AF:

0.000658

AC:

AN:

33454

American (AMR)

AF:

0.00222

AC:

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.00464

AC:

121

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39606

South Asian (SAS)

AF:

0.0146

AC:

1249

AN:

85662

European-Finnish (FIN)

AF:

0.00208

AC:

111

AN:

53374

Middle Eastern (MID)

AF:

0.00781

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00440

AC:

4888

AN:

1111136

Other (OTH)

AF:

0.00565

AC:

341

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

307

614

921

1228

1535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00351

AC:

535

AN:

152334

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.000649

AC:

AN:

41584

American (AMR)

AF:

0.00222

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00720

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.0143

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00198

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00516

AC:

351

AN:

68024

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00295

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000275

AC:

ESP6500EA

AF:

0.00405

AC:

ExAC

AF:

0.00498

AC:

602

Asia WGS

AF:

0.00289

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

0.10

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;.;.;.;.;.;.;.;.;.;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;T;T;T;T;T;T;T;T;T;T;T

MetaRNN

Benign

0.011

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.3

M;.;M;.;.;.;.;.;.;.;.;.

PhyloP100

4.3

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-4.0

.;.;D;.;D;.;.;.;.;.;.;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0010

.;.;D;.;D;.;.;.;.;.;.;D

Sift4G

Uncertain

0.0020

.;.;D;.;D;.;.;.;.;.;.;D

Polyphen

0.79

P;.;.;.;.;.;.;.;.;.;.;P

Vest4

0.72, 0.64, 0.64

MVP

0.76

MPC

0.15

ClinPred

0.046

GERP RS

4.2

Varity_R

0.55

gMVP

0.89

Mutation Taster

=93/7

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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11-31539740-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over