rs2996470

Variant names:

• chr11-31538111-G-A
• rs2996470
• NM_019040.5:c.260-1551G>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.260-1551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.361 in 151,334 control chromosomes in the GnomAD database, including 12,109 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 (12109 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• 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 (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.260-1551G>A		intron_variant	Intron 2 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.260-1551G>A		intron_variant	Intron 2 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.260-1551G>A		intron_variant	Intron 2 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.260-1551G>A		intron_variant	Intron 2 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54463 AN: 151226 Hom.: 12058 Cov.: 32

Gnomad AFR AF: 0.625

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.368

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.361 AC: 54574 AN: 151334 Hom.: 12109 Cov.: 32 AF XY: 0.355 AC XY: 26233 AN XY: 73952

African (AFR) AF: 0.625 AC: 25796 AN: 41252

American (AMR) AF: 0.382 AC: 5808 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1070 AN: 3466

East Asian (EAS) AF: 0.332 AC: 1712 AN: 5152

South Asian (SAS) AF: 0.342 AC: 1640 AN: 4796

European-Finnish (FIN) AF: 0.117 AC: 1212 AN: 10360

Middle Eastern (MID) AF: 0.306 AC: 87 AN: 284

European-Non Finnish (NFE) AF: 0.240 AC: 16263 AN: 67812

Other (OTH) AF: 0.377 AC: 790 AN: 2098

Alfa AF: 0.325 Hom.: 1611

Bravo AF: 0.391

Asia WGS AF: 0.388 AC: 1344 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.43
PhyloP100		-0.54
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: rs2996470; hg19: chr11-31559658;