rs2146569

Variant names:

• chr11-31587561-C-A
• rs2146569
• NM_019040.5:c.382-7209C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-31587561-C-A
• chr11-31587561-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019040.5(ELP4):​c.382-7209C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,016 control chromosomes in the GnomAD database, including 33,359 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 (33359 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.382-7209C>A		intron_variant	Intron 3 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.382-7209C>A		intron_variant	Intron 3 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.382-7209C>A		intron_variant	Intron 3 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.382-7209C>A		intron_variant	Intron 3 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97211 AN: 151898 Hom.: 33363 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.683

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: 0.639 AC: 97214 AN: 152016 Hom.: 33359 Cov.: 32 AF XY: 0.646 AC XY: 47958 AN XY: 74292

African (AFR) AF: 0.375 AC: 15528 AN: 41400

American (AMR) AF: 0.617 AC: 9425 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2395 AN: 3466

East Asian (EAS) AF: 0.668 AC: 3455 AN: 5174

South Asian (SAS) AF: 0.658 AC: 3170 AN: 4814

European-Finnish (FIN) AF: 0.883 AC: 9355 AN: 10590

Middle Eastern (MID) AF: 0.700 AC: 203 AN: 290

European-Non Finnish (NFE) AF: 0.760 AC: 51650 AN: 67984

Other (OTH) AF: 0.624 AC: 1317 AN: 2110

Alfa AF: 0.677 Hom.: 4747

Bravo AF: 0.608

Asia WGS AF: 0.611 AC: 2122 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.24
PhyloP100		-2.1
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: rs2146569; hg19: chr11-31609108;