11-31509801-C-G

Variant names:

• chr11-31509801-C-G
• rs760224399
• NM_019040.5:c.17C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_019040.5(ELP4):​c.17C>G​(p.Thr6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,808 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T6I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061472744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.17C>G	p.Thr6Ser	missense_variant	Exon 1 of 10	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.17C>G	p.Thr6Ser	missense_variant	Exon 1 of 12		NP_001275655.1
ELP4	NM_001288725.2	c.17C>G	p.Thr6Ser	missense_variant	Exon 1 of 11		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.17C>G	p.Thr6Ser	missense_variant	Exon 1 of 10	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 249284 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135278

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad SAS exome AF: 0.0000654

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461808 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727190

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: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.012	T;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.56	T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.061	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.;L;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.42	.;.;N;.;N;.;.;.;.;.;.;.;N
REVEL	Benign	0.013
Sift	Benign	0.16	.;.;T;.;T;.;.;.;.;.;.;.;D
Sift4G	Benign	0.26	.;.;T;.;T;.;.;.;.;.;.;.;T
Polyphen		0.0030	B;.;.;.;.;.;.;.;.;.;.;.;B
Vest4		0.16, 0.15, 0.13
MutPred		0.16		Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);Gain of sheet (P = 0.0477);
MVP		0.25
MPC		0.048
ClinPred		0.031	T
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.040
gMVP		0.28

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: rs760224399; hg19: chr11-31531348;