rs2273943

Variant names:

• chr11-31626982-G-A
• rs2273943
• NM_019040.5:c.654-128G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• aniridia 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp
• aniridia 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000228061 (HGNC:58222):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.654-128G>A		intron_variant	Intron 5 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.654-128G>A		intron_variant	Intron 5 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.657-128G>A		intron_variant	Intron 5 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.654-128G>A		intron_variant	Intron 5 of 9	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

African (AFR) AF: 0.358 AC: 3928 AN: 10958

American (AMR) AF: 0.589 AC: 10877 AN: 18472

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 8609 AN: 12294

East Asian (EAS) AF: 0.647 AC: 18164 AN: 28056

South Asian (SAS) AF: 0.648 AC: 20344 AN: 31386

European-Finnish (FIN) AF: 0.870 AC: 35570 AN: 40908

Middle Eastern (MID) AF: 0.679 AC: 1238 AN: 1824

European-Non Finnish (NFE) AF: 0.760 AC: 180634 AN: 237630

Other (OTH) AF: 0.706 AC: 16166 AN: 22908

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

African (AFR) AF: 0.360 AC: 14897 AN: 41352

American (AMR) AF: 0.617 AC: 9366 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2393 AN: 3464

East Asian (EAS) AF: 0.665 AC: 3413 AN: 5134

South Asian (SAS) AF: 0.656 AC: 3163 AN: 4822

European-Finnish (FIN) AF: 0.884 AC: 9344 AN: 10572

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51532 AN: 67802

Other (OTH) AF: 0.619 AC: 1301 AN: 2102

Alfa AF: 0.674 Hom.: 4733

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2273943; hg19: chr11-31648529;