11-31657400-C-A

Variant names:

• chr11-31657400-C-A
• rs964112
• NM_019040.5:c.1143+7179C>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.1143+7179C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,816 control chromosomes in the GnomAD database, including 8,591 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 0.30 (8591 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.241
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.1143+7179C>A		intron_variant	Intron 9 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.1143+7179C>A		intron_variant	Intron 9 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.1146+7179C>A		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+7179C>A		intron_variant	Intron 9 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46107 AN: 151698 Hom.: 8594 Cov.: 32

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.295

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

GnomAD4 genome AF: 0.304 AC: 46099 AN: 151816 Hom.: 8591 Cov.: 32 AF XY: 0.310 AC XY: 22959 AN XY: 74150

African (AFR) AF: 0.0768 AC: 3188 AN: 41484

American (AMR) AF: 0.323 AC: 4904 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3466

East Asian (EAS) AF: 0.451 AC: 2321 AN: 5144

South Asian (SAS) AF: 0.356 AC: 1713 AN: 4816

European-Finnish (FIN) AF: 0.492 AC: 5193 AN: 10560

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26795 AN: 67834

Other (OTH) AF: 0.291 AC: 612 AN: 2106

Alfa AF: 0.341 Hom.: 3839

Bravo AF: 0.280

Asia WGS AF: 0.338 AC: 1178 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.32
PhyloP100		0.24
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: rs964112; hg19: chr11-31678948;