11-31539728-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_019040.5(ELP4):c.326A>G(p.Asn109Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,612,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0140

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06978315).
• BP6: Variant 11-31539728-A-G is Benign according to our data. Variant chr11-31539728-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2391737.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP4	NM_019040.5	c.326A>G	p.Asn109Ser	missense_variant	3/10	ENST00000640961.2
ELP4	NM_001288726.2	c.326A>G	p.Asn109Ser	missense_variant	3/12
ELP4	NM_001288725.2	c.326A>G	p.Asn109Ser	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP4	ENST00000640961.2	c.326A>G	p.Asn109Ser	missense_variant	3/10	1	NM_019040.5	P3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

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

GnomAD3 exomes AF: 0.0000161 AC: 4 AN: 248460 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134772

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.00000685 AC: 10 AN: 1460070 Hom.: 0 Cov.: 30 AF XY: 0.00000688 AC XY: 5 AN XY: 726258

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152188 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74350

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.0000549

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.051
Dann	Benign	0.20
DEOGEN2	Benign	0.0080	T;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.099	N
LIST_S2	Benign	0.78	T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.070	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N;.;N;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.25	T
Polyphen		0.0010	B;.;.;.;.;.;.;.;.;.;.;B
Vest4		0.051, 0.050, 0.055
MutPred		0.66		Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);Gain of glycosylation at N109 (P = 0.0772);
MVP		0.28
MPC		0.044
ClinPred		0.012	T
GERP RS		-11
Varity_R		0.022
gMVP		0.14

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

Other links and lift over

dbSNP: rs748375028; hg19: chr11-31561275;