chr11-31631665-G-A

Variant names:

• chr11-31631665-G-A
• rs11031434
• NM_019040.5:c.739-552G>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.739-552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,964 control chromosomes in the GnomAD database, including 12,114 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 0.36 (12114 hom., cov: 33)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.739-552G>A		intron_variant	Intron 6 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.739-552G>A		intron_variant	Intron 6 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.742-552G>A		intron_variant	Intron 6 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.739-552G>A		intron_variant	Intron 6 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55364 AN: 151846 Hom.: 12118 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.364 AC: 55351 AN: 151964 Hom.: 12114 Cov.: 33 AF XY: 0.373 AC XY: 27708 AN XY: 74262

African (AFR) AF: 0.117 AC: 4835 AN: 41488

American (AMR) AF: 0.364 AC: 5554 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3470

East Asian (EAS) AF: 0.628 AC: 3235 AN: 5152

South Asian (SAS) AF: 0.453 AC: 2178 AN: 4812

European-Finnish (FIN) AF: 0.584 AC: 6173 AN: 10578

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.455 AC: 30928 AN: 67908

Other (OTH) AF: 0.363 AC: 766 AN: 2110

Alfa AF: 0.394 Hom.: 1776

Bravo AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		-0.39
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: rs11031434; hg19: chr11-31653212;