chr11-31525680-G-T

Variant names:

• chr11-31525680-G-T
• rs502794
• NM_019040.5:c.259+5589G>T

Variant summary

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

The NM_019040.5(ELP4):​c.259+5589G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 151,900 control chromosomes in the GnomAD database, including 32,759 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 (32759 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.575
• 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
• ocular dysgenesis caused by defects in PAX6 regulation

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	NM_019040.5	MANE Select	c.259+5589G>T		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.259+5589G>T		intron	N/A	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.259+5589G>T		intron	N/A	NP_001275654.1	Q96EB1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	ENST00000640961.2	TSL:1 MANE Select	c.259+5589G>T		intron	N/A	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.259+5589G>T		intron	N/A	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.259+5589G>T		intron	N/A	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96876 AN: 151782 Hom.: 32703 Cov.: 31

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.639 AC: 96994 AN: 151900 Hom.: 32759 Cov.: 31 AF XY: 0.630 AC XY: 46732 AN XY: 74206

African (AFR) AF: 0.871 AC: 36120 AN: 41490

American (AMR) AF: 0.646 AC: 9859 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.622 AC: 2158 AN: 3468

East Asian (EAS) AF: 0.368 AC: 1892 AN: 5140

South Asian (SAS) AF: 0.549 AC: 2640 AN: 4812

European-Finnish (FIN) AF: 0.420 AC: 4412 AN: 10512

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37699 AN: 67900

Other (OTH) AF: 0.642 AC: 1353 AN: 2108

Alfa AF: 0.573 Hom.: 23693

Bravo AF: 0.665

Asia WGS AF: 0.509 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	12
DANN	Benign	0.61
PhyloP100		0.57
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs502794;

hg19: chr11-31547227;