rs2273943

Positions:

• chr11-31626982-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.654-128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 556,074 control chromosomes in the GnomAD database, including 143,164 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 (33047 hom., cov: 31)
  • Exomes 𝑓: 0.73 (110117 hom.)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP4	NM_019040.5	c.654-128G>A		intron_variant		ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.654-128G>A		intron_variant			NP_001275655.1
ELP4	NM_001288725.2	c.657-128G>A		intron_variant			NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.654-128G>A		intron_variant		1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96329 AN: 151520 Hom.: 33052 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.731 AC: 295530 AN: 404436 Hom.: 110117 AF XY: 0.730 AC XY: 156378 AN XY: 214298

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.589

Gnomad4 ASJ exome AF: 0.700

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.648

Gnomad4 FIN exome AF: 0.870

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.635 AC: 96331 AN: 151638 Hom.: 33047 Cov.: 31 AF XY: 0.641 AC XY: 47475 AN XY: 74068

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.619

Alfa AF: 0.686 Hom.: 4675

Bravo AF: 0.604

Asia WGS AF: 0.607 AC: 2101 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.12
DANN	Benign	0.48

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: rs2273943; hg19: chr11-31648529;