rs2146569

Positions:

• chr11-31587561-C-A
• chr11-31587561-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019040.5(ELP4):​c.382-7209C>A 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 152,016 control chromosomes in the GnomAD database, including 33,359 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 (33359 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP4	NM_019040.5	c.382-7209C>A		intron_variant		ENST00000640961.2
ELP4	NM_001288725.2	c.382-7209C>A		intron_variant
ELP4	NM_001288726.2	c.382-7209C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP4	ENST00000640961.2	c.382-7209C>A		intron_variant		1	NM_019040.5	P3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97211 AN: 151898 Hom.: 33363 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.683

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.639 AC: 97214 AN: 152016 Hom.: 33359 Cov.: 32 AF XY: 0.646 AC XY: 47958 AN XY: 74292

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.658

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.624

Alfa AF: 0.688 Hom.: 4685

Bravo AF: 0.608

Asia WGS AF: 0.611 AC: 2122 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.24

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

Publications

LitVar

Other links and lift over

dbSNP: rs2146569; hg19: chr11-31609108;