11-31597303-T-A

Position:

• chr11-31597303-T-A

Variant summary

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

The NM_019040.5(ELP4):​c.513+2402T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,022 control chromosomes in the GnomAD database, including 33,398 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 (33398 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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 (NFE) allele frequency at 95% confidence interval = 0.755 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ELP4	NM_019040.5	c.513+2402T>A		intron_variant		ENST00000640961.2
ELP4	NM_001288725.2	c.513+2402T>A		intron_variant
ELP4	NM_001288726.2	c.513+2402T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ELP4	ENST00000640961.2	c.513+2402T>A		intron_variant		1	NM_019040.5	P3

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97224 AN: 151904 Hom.: 33402 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.684

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: 0.640 AC: 97228 AN: 152022 Hom.: 33398 Cov.: 31 AF XY: 0.645 AC XY: 47956 AN XY: 74298

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.617

Gnomad4 ASJ AF: 0.690

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.884

Gnomad4 NFE AF: 0.760

Gnomad4 OTH AF: 0.624

Alfa AF: 0.689 Hom.: 4692

Bravo AF: 0.608

Asia WGS AF: 0.608 AC: 2114 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	2.5
DANN	Benign	0.61

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: rs10835793; hg19: chr11-31618850;