11-31674788-A-G

Variant names:

• chr11-31674788-A-G
• rs2862801
• NM_019040.5:c.1143+24567A>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.1143+24567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,126 control chromosomes in the GnomAD database, including 33,137 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 0.64 (33137 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.426
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.1143+24567A>G		intron_variant	Intron 9 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.1144-6999A>G		intron_variant	Intron 9 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.1146+24567A>G		intron_variant	Intron 9 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.1143+24567A>G		intron_variant	Intron 9 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96605 AN: 152008 Hom.: 33142 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.635 AC: 96607 AN: 152126 Hom.: 33137 Cov.: 32 AF XY: 0.641 AC XY: 47663 AN XY: 74386

African (AFR) AF: 0.360 AC: 14940 AN: 41482

American (AMR) AF: 0.615 AC: 9403 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2396 AN: 3470

East Asian (EAS) AF: 0.667 AC: 3448 AN: 5166

South Asian (SAS) AF: 0.657 AC: 3167 AN: 4824

European-Finnish (FIN) AF: 0.884 AC: 9371 AN: 10606

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51650 AN: 67974

Other (OTH) AF: 0.620 AC: 1311 AN: 2114

Alfa AF: 0.719 Hom.: 20532

Bravo AF: 0.604

Asia WGS AF: 0.610 AC: 2122 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.62
PhyloP100		0.43
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: rs2862801; hg19: chr11-31696336;