Variant 11-31539740-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr11-31539740-T-C is described in Lovd as [Benign].

BS2

High AC in GnomAd4 at 535 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ELP4	NM_019040.5 linkuse as main transcript	c.338T>C	p.Leu113Ser	missense_variant	3/10	ENST00000640961.2
ELP4	NM_001288726.2 linkuse as main transcript	c.338T>C	p.Leu113Ser	missense_variant	3/12
ELP4	NM_001288725.2 linkuse as main transcript	c.338T>C	p.Leu113Ser	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP4	ENST00000640961.2 linkuse as main transcript	c.338T>C	p.Leu113Ser	missense_variant	3/10	1	NM_019040.5	P3	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

GnomAD3 exomes

AF:

0.00476

AC:

1181

AN:

248216

Hom.:

AF XY:

0.00530

AC XY:

714

AN XY:

134604

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 SAS exome

AF:

0.0157

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

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.00464

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0146

Gnomad4 FIN exome

AF:

0.00208

Gnomad4 NFE exome

AF:

0.00440

Gnomad4 OTH exome

AF:

0.00565

GnomAD4 genome

AF:

0.00351

AC:

535

AN:

152334

Hom.:

Cov.:

AF XY:

0.00357

AC XY:

266

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00516

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00420

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

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

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;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over