rs10835810

Variant names:

• chr11-31700936-C-T
• rs10835810
• NM_019040.5:c.1143+50715C>T

Variant summary

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

The NM_019040.5(ELP4):​c.1143+50715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,856 control chromosomes in the GnomAD database, including 8,637 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 0.30 (8637 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019040.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	NM_019040.5	MANE Select	c.1143+50715C>T		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.1432+18861C>T		intron	N/A	NP_001275655.1
	ELP4	NM_001288725.2		c.1146+50715C>T		intron	N/A	NP_001275654.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	ENST00000640961.2	TSL:1 MANE Select	c.1143+50715C>T		intron	N/A	ENSP00000492152.1
	ELP4	ENST00000395934.2	TSL:1	c.1432+18861C>T		intron	N/A	ENSP00000379267.2
	ELP4	ENST00000379163.10	TSL:2	c.1146+50715C>T		intron	N/A	ENSP00000368461.5

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46246 AN: 151738 Hom.: 8640 Cov.: 31

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.304 AC: 46238 AN: 151856 Hom.: 8637 Cov.: 31 AF XY: 0.310 AC XY: 23020 AN XY: 74174

African (AFR) AF: 0.0771 AC: 3197 AN: 41484

American (AMR) AF: 0.324 AC: 4934 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1107 AN: 3462

East Asian (EAS) AF: 0.452 AC: 2327 AN: 5150

South Asian (SAS) AF: 0.356 AC: 1705 AN: 4794

European-Finnish (FIN) AF: 0.492 AC: 5182 AN: 10528

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26888 AN: 67886

Other (OTH) AF: 0.292 AC: 614 AN: 2106

Alfa AF: 0.377 Hom.: 10791

Bravo AF: 0.281

Asia WGS AF: 0.337 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		-0.13
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: rs10835810; hg19: chr11-31722484;