chr11-31567652-A-G

Variant names:

• chr11-31567652-A-G
• rs2996464
• NM_019040.5:c.382-27118A>G

Variant summary

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

The NM_019040.5(ELP4):​c.382-27118A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,122 control chromosomes in the GnomAD database, including 5,254 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 0.25 (5254 hom., cov: 32)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• 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
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.312 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.382-27118A>G		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.382-27118A>G		intron	N/A	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.382-27118A>G		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.382-27118A>G		intron	N/A	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.382-27118A>G		intron	N/A	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.382-27118A>G		intron	N/A	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37866 AN: 152004 Hom.: 5254 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.0371

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.249 AC: 37866 AN: 152122 Hom.: 5254 Cov.: 32 AF XY: 0.246 AC XY: 18323 AN XY: 74362

African (AFR) AF: 0.146 AC: 6079 AN: 41542

American (AMR) AF: 0.250 AC: 3823 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3466

East Asian (EAS) AF: 0.0372 AC: 193 AN: 5184

South Asian (SAS) AF: 0.206 AC: 992 AN: 4816

European-Finnish (FIN) AF: 0.302 AC: 3187 AN: 10566

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21415 AN: 67964

Other (OTH) AF: 0.246 AC: 520 AN: 2116

Alfa AF: 0.292 Hom.: 26307

Bravo AF: 0.241

Asia WGS AF: 0.114 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.1
DANN	Benign	0.57
PhyloP100		0.049
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: rs2996464; hg19: chr11-31589199;