rs2996470

Positions:

• chr11-31538111-G-A

Variant summary

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

The NM_019040.5(ELP4):​c.260-1551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,334 control chromosomes in the GnomAD database, including 12,109 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 (12109 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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 (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP4	NM_019040.5	c.260-1551G>A		intron_variant		ENST00000640961.2
ELP4	NM_001288725.2	c.260-1551G>A		intron_variant
ELP4	NM_001288726.2	c.260-1551G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP4	ENST00000640961.2	c.260-1551G>A		intron_variant		1	NM_019040.5	P3

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54463 AN: 151226 Hom.: 12058 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.368

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

GnomAD4 genome AF: 0.361 AC: 54574 AN: 151334 Hom.: 12109 Cov.: 32 AF XY: 0.355 AC XY: 26233 AN XY: 73952

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.377

Alfa AF: 0.316 Hom.: 1466

Bravo AF: 0.391

Asia WGS AF: 0.388 AC: 1344 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.43

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: rs2996470; hg19: chr11-31559658;