NM_019040.5:c.653+11027G>A

Variant names:

• chr11-31614934-G-A
• rs986527
• NM_019040.5:c.653+11027G>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.653+11027G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,944 control chromosomes in the GnomAD database, including 8,583 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 (8583 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.653+11027G>A		intron_variant	Intron 5 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.653+11027G>A		intron_variant	Intron 5 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.656+11027G>A		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+11027G>A		intron_variant	Intron 5 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46106 AN: 151826 Hom.: 8586 Cov.: 31

Gnomad AFR AF: 0.0770

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.303 AC: 46098 AN: 151944 Hom.: 8583 Cov.: 31 AF XY: 0.309 AC XY: 22958 AN XY: 74244

African (AFR) AF: 0.0768 AC: 3187 AN: 41496

American (AMR) AF: 0.321 AC: 4892 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1087 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2324 AN: 5160

South Asian (SAS) AF: 0.356 AC: 1719 AN: 4824

European-Finnish (FIN) AF: 0.490 AC: 5159 AN: 10526

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

European-Non Finnish (NFE) AF: 0.395 AC: 26829 AN: 67902

Other (OTH) AF: 0.293 AC: 617 AN: 2108

Alfa AF: 0.334 Hom.: 19647

Bravo AF: 0.280

Asia WGS AF: 0.337 AC: 1172 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.52
PhyloP100		-1.2
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: rs986527; hg19: chr11-31636481;