rs1232203

Variant names:

• chr11-31644660-G-T
• rs1232203
• NM_019040.5:c.928-3081G>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.928-3081G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,452 control chromosomes in the GnomAD database, including 4,786 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 0.24 (4786 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.551
• 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
• 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=-0.88).
• 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.928-3081G>T		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.928-3081G>T		intron	N/A	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.931-3081G>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.928-3081G>T		intron	N/A	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.928-3081G>T		intron	N/A	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.931-3081G>T		intron	N/A	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35870 AN: 151334 Hom.: 4786 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.0370

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.237 AC: 35864 AN: 151452 Hom.: 4786 Cov.: 32 AF XY: 0.235 AC XY: 17373 AN XY: 73934

African (AFR) AF: 0.129 AC: 5344 AN: 41374

American (AMR) AF: 0.238 AC: 3600 AN: 15134

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3464

East Asian (EAS) AF: 0.0370 AC: 190 AN: 5130

South Asian (SAS) AF: 0.203 AC: 979 AN: 4816

European-Finnish (FIN) AF: 0.302 AC: 3167 AN: 10496

Middle Eastern (MID) AF: 0.278 AC: 80 AN: 288

European-Non Finnish (NFE) AF: 0.302 AC: 20474 AN: 67740

Other (OTH) AF: 0.231 AC: 486 AN: 2100

Alfa AF: 0.258 Hom.: 876

Bravo AF: 0.227

Asia WGS AF: 0.106 AC: 366 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.050
DANN	Benign	0.34
PhyloP100		-0.55
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1232203;

hg19: chr11-31666208;