rs509628

Variant names:

• chr11-31513808-G-A
• rs509628
• NM_019040.5:c.223+3801G>A

Variant summary

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

The NM_019040.5(ELP4):​c.223+3801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,068 control chromosomes in the GnomAD database, including 33,390 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 (33390 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 10 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.223+3801G>A		intron_variant	Intron 1 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.223+3801G>A		intron_variant	Intron 1 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.223+3801G>A		intron_variant	Intron 1 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.223+3801G>A		intron_variant	Intron 1 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97631 AN: 151950 Hom.: 33322 Cov.: 32

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.642

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

GnomAD4 genome AF: 0.643 AC: 97762 AN: 152068 Hom.: 33390 Cov.: 32 AF XY: 0.634 AC XY: 47098 AN XY: 74326

African (AFR) AF: 0.886 AC: 36781 AN: 41522

American (AMR) AF: 0.647 AC: 9880 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2160 AN: 3468

East Asian (EAS) AF: 0.367 AC: 1898 AN: 5174

South Asian (SAS) AF: 0.547 AC: 2642 AN: 4826

European-Finnish (FIN) AF: 0.420 AC: 4426 AN: 10532

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37747 AN: 67960

Other (OTH) AF: 0.646 AC: 1365 AN: 2112

Alfa AF: 0.584 Hom.: 18538

Bravo AF: 0.670

Asia WGS AF: 0.513 AC: 1776 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.075
DANN	Benign	0.37
PhyloP100		-0.44
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: rs509628; hg19: chr11-31535355;