rs2973127

Positions:

• chr11-31541471-A-G

Variant summary

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

The NM_019040.5(ELP4):​c.381+1688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,106 control chromosomes in the GnomAD database, including 12,158 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 (12158 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP4	NM_019040.5	c.381+1688A>G		intron_variant		ENST00000640961.2
ELP4	NM_001288725.2	c.381+1688A>G		intron_variant
ELP4	NM_001288726.2	c.381+1688A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP4	ENST00000640961.2	c.381+1688A>G		intron_variant		1	NM_019040.5	P3

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54659 AN: 151988 Hom.: 12106 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.367

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.360 AC: 54774 AN: 152106 Hom.: 12158 Cov.: 32 AF XY: 0.354 AC XY: 26338 AN XY: 74382

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.330

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.376

Alfa AF: 0.291 Hom.: 1547

Bravo AF: 0.391

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2973127; hg19: chr11-31563018;