11-31539685-TC-T

Variant names:

• chr11-31539685-TC-T
• rs754625061
• NM_019040.5:c.284delC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_019040.5(ELP4):​c.284delC​(p.Ser95TyrfsTer64) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000137 in 1,455,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as association (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ELP4 NM_019040.5 frameshift
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 7.03
• 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.284delC	p.Ser95TyrfsTer64	frameshift	Exon 3 of 10	NP_061913.3
	ELP4	NM_001288726.2		c.284delC	p.Ser95TyrfsTer64	frameshift	Exon 3 of 12	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.284delC	p.Ser95TyrfsTer64	frameshift	Exon 3 of 11	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.284delC	p.Ser95TyrfsTer64	frameshift	Exon 3 of 10	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.284delC	p.Ser95TyrfsTer64	frameshift	Exon 3 of 12	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.284delC	p.Ser95TyrfsTer64	frameshift	Exon 3 of 11	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000814 AC: 2 AN: 245550 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455222 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723504

African (AFR) AF: 0.00 AC: 0 AN: 33318

American (AMR) AF: 0.00 AC: 0 AN: 43910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 84274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1109038

Other (OTH) AF: 0.00 AC: 0 AN: 60148

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Autism spectrum disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.0
Mutation Taster		=14/186	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs754625061; hg19: chr11-31561232;