rs12365798

Variant names:

• chr11-31726210-T-C
• rs12365798
• NM_019040.5:c.1144-57183T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019040.5(ELP4):​c.1144-57183T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,920 control chromosomes in the GnomAD database, including 7,518 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (7518 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 1 publications found

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)

ENSG00000228061 (HGNC:58222):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.1144-57183T>C		intron_variant	Intron 9 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.1433-37201T>C		intron_variant	Intron 10 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.1147-37201T>C		intron_variant	Intron 9 of 10		NP_001275654.1
ELP4-AS1	NR_199065.1	n.410-36770A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.1144-57183T>C		intron_variant	Intron 9 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45751 AN: 151804 Hom.: 7496 Cov.: 31

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.302 AC: 45807 AN: 151920 Hom.: 7518 Cov.: 31 AF XY: 0.297 AC XY: 22068 AN XY: 74280

African (AFR) AF: 0.435 AC: 18023 AN: 41394

American (AMR) AF: 0.275 AC: 4203 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3472

East Asian (EAS) AF: 0.309 AC: 1587 AN: 5142

South Asian (SAS) AF: 0.342 AC: 1645 AN: 4814

European-Finnish (FIN) AF: 0.135 AC: 1429 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.248 AC: 16867 AN: 67942

Other (OTH) AF: 0.331 AC: 700 AN: 2114

Alfa AF: 0.285 Hom.: 860

Bravo AF: 0.314

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.3
DANN	Benign	0.78
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12365798; hg19: chr11-31747758;