rs2863231

Variant names:

• chr11-31775012-A-G
• rs2863231
• NM_019040.5:c.1144-8381A>G

Variant summary

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

The NM_019040.5(ELP4):​c.1144-8381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 152,026 control chromosomes in the GnomAD database, including 39,240 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 0.71 (39240 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 7 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019040.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	NM_019040.5	MANE Select	c.1144-8381A>G		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.1572-8381A>G		intron	N/A	NP_001275655.1
	ELP4	NM_001288725.2		c.1286-8381A>G		intron	N/A	NP_001275654.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	ENST00000640961.2	TSL:1 MANE Select	c.1144-8381A>G		intron	N/A	ENSP00000492152.1
	ELP4	ENST00000395934.2	TSL:1	c.1572-8381A>G		intron	N/A	ENSP00000379267.2
	ELP4	ENST00000379163.10	TSL:2	c.1286-8381A>G		intron	N/A	ENSP00000368461.5

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107285 AN: 151908 Hom.: 39171 Cov.: 31

Gnomad AFR AF: 0.901

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.707 AC: 107415 AN: 152026 Hom.: 39240 Cov.: 31 AF XY: 0.698 AC XY: 51875 AN XY: 74318

African (AFR) AF: 0.902 AC: 37409 AN: 41494

American (AMR) AF: 0.622 AC: 9492 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2489 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2211 AN: 5156

South Asian (SAS) AF: 0.688 AC: 3309 AN: 4812

European-Finnish (FIN) AF: 0.543 AC: 5727 AN: 10544

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44316 AN: 67964

Other (OTH) AF: 0.726 AC: 1533 AN: 2112

Alfa AF: 0.675 Hom.: 46058

Bravo AF: 0.716

Asia WGS AF: 0.590 AC: 2057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.77
PhyloP100		-0.32
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: rs2863231; hg19: chr11-31796560;