11-31552099-T-C

Variant names:

• chr11-31552099-T-C
• rs2104246
• NM_019040.5:c.381+12316T>C

Variant summary

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

The NM_019040.5(ELP4):​c.381+12316T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,988 control chromosomes in the GnomAD database, including 13,013 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 0.37 (13013 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.381+12316T>C		intron_variant	Intron 3 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.381+12316T>C		intron_variant	Intron 3 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.381+12316T>C		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.381+12316T>C		intron_variant	Intron 3 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55971 AN: 151870 Hom.: 12960 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.369 AC: 56089 AN: 151988 Hom.: 13013 Cov.: 32 AF XY: 0.363 AC XY: 26984 AN XY: 74304

African (AFR) AF: 0.657 AC: 27204 AN: 41422

American (AMR) AF: 0.384 AC: 5850 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1073 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1704 AN: 5164

South Asian (SAS) AF: 0.341 AC: 1643 AN: 4816

European-Finnish (FIN) AF: 0.116 AC: 1232 AN: 10602

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16288 AN: 67954

Other (OTH) AF: 0.384 AC: 812 AN: 2114

Alfa AF: 0.307 Hom.: 3635

Bravo AF: 0.401

Asia WGS AF: 0.389 AC: 1351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.72
PhyloP100		-0.24
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: rs2104246; hg19: chr11-31573646;