NM_019040.5:c.653+7114A>T

Variant names:

• chr11-31611021-A-T
• rs1232182
• NM_019040.5:c.653+7114A>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.653+7114A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,030 control chromosomes in the GnomAD database, including 4,868 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 0.23 (4868 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.653+7114A>T		intron_variant	Intron 5 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.653+7114A>T		intron_variant	Intron 5 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.656+7114A>T		intron_variant	Intron 5 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.653+7114A>T		intron_variant	Intron 5 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34387 AN: 151912 Hom.: 4869 Cov.: 32

Gnomad AFR AF: 0.0673

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.226 AC: 34378 AN: 152030 Hom.: 4868 Cov.: 32 AF XY: 0.224 AC XY: 16641 AN XY: 74282

African (AFR) AF: 0.0671 AC: 2783 AN: 41488

American (AMR) AF: 0.243 AC: 3701 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1077 AN: 3468

East Asian (EAS) AF: 0.0371 AC: 192 AN: 5174

South Asian (SAS) AF: 0.206 AC: 995 AN: 4824

European-Finnish (FIN) AF: 0.303 AC: 3200 AN: 10552

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21378 AN: 67956

Other (OTH) AF: 0.226 AC: 476 AN: 2106

Alfa AF: 0.261 Hom.: 708

Bravo AF: 0.215

Asia WGS AF: 0.113 AC: 394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.80
PhyloP100		-0.18
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: rs1232182; hg19: chr11-31632568;