11-31680968-G-T

Variant names:

• chr11-31680968-G-T
• rs10488689
• NM_019040.5:c.1143+30747G>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+30747G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,972 control chromosomes in the GnomAD database, including 4,530 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 0.22 (4530 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.983
• Publications: 0 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
• ocular dysgenesis caused by defects in PAX6 regulation

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• aniridia 1

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

ELP4-AS1 (HGNC:58222):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	NM_019040.5	MANE Select	c.1143+30747G>T		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.1144-819G>T		intron	N/A	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.1146+30747G>T		intron	N/A	NP_001275654.1	Q96EB1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	ENST00000640961.2	TSL:1 MANE Select	c.1143+30747G>T		intron	N/A	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.1144-819G>T		intron	N/A	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.1146+30747G>T		intron	N/A	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33161 AN: 151852 Hom.: 4531 Cov.: 32

Gnomad AFR AF: 0.0652

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.218 AC: 33152 AN: 151972 Hom.: 4530 Cov.: 32 AF XY: 0.217 AC XY: 16093 AN XY: 74268

African (AFR) AF: 0.0650 AC: 2695 AN: 41470

American (AMR) AF: 0.230 AC: 3518 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1069 AN: 3464

East Asian (EAS) AF: 0.0371 AC: 192 AN: 5182

South Asian (SAS) AF: 0.202 AC: 971 AN: 4806

European-Finnish (FIN) AF: 0.303 AC: 3183 AN: 10514

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20516 AN: 67940

Other (OTH) AF: 0.214 AC: 453 AN: 2114

Alfa AF: 0.251 Hom.: 2430

Bravo AF: 0.206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.023
DANN	Benign	0.22
PhyloP100		-0.98
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: rs10488689; hg19: chr11-31702516;