11-31619914-A-G

Variant names:

• chr11-31619914-A-G
• rs7947424
• NM_019040.5:c.654-7196A>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.654-7196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,826 control chromosomes in the GnomAD database, including 33,089 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 0.64 (33089 hom., cov: 30)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.74
• 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
• 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=-1.1).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 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.654-7196A>G		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.654-7196A>G		intron	N/A	NP_001275655.1
	ELP4	NM_001288725.2		c.657-7196A>G		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.654-7196A>G		intron	N/A	ENSP00000492152.1
	ELP4	ENST00000395934.2	TSL:1	c.654-7196A>G		intron	N/A	ENSP00000379267.2
	ENSG00000228061	ENST00000648611.1		n.2155T>C		non_coding_transcript_exon	Exon 10 of 10

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96439 AN: 151708 Hom.: 33094 Cov.: 30

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.635 AC: 96441 AN: 151826 Hom.: 33089 Cov.: 30 AF XY: 0.641 AC XY: 47550 AN XY: 74182

African (AFR) AF: 0.360 AC: 14911 AN: 41396

American (AMR) AF: 0.617 AC: 9383 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2391 AN: 3464

East Asian (EAS) AF: 0.664 AC: 3411 AN: 5134

South Asian (SAS) AF: 0.657 AC: 3163 AN: 4814

European-Finnish (FIN) AF: 0.883 AC: 9363 AN: 10598

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51593 AN: 67900

Other (OTH) AF: 0.620 AC: 1304 AN: 2104

Alfa AF: 0.664 Hom.: 5378

Bravo AF: 0.604

Asia WGS AF: 0.608 AC: 2116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.71
DANN	Benign	0.40
PhyloP100		-2.7
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: rs7947424; hg19: chr11-31641461;