rs4922571

Variant names:

• chr11-31664901-G-A
• rs4922571
• NM_019040.5:c.1143+14680G>A

Variant summary

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

The ENST00000640961.2(ELP4):​c.1143+14680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 151,978 control chromosomes in the GnomAD database, including 31,735 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 0.61 (31735 hom., cov: 32)
• Consequence: ELP4 ENST00000640961.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 2 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=-0.9).
• 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: ENST00000640961.2. 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.1143+14680G>A		intron	N/A	NP_061913.3
	ELP4	NM_001288726.2		c.1143+14680G>A		intron	N/A	NP_001275655.1
	ELP4	NM_001288725.2		c.1146+14680G>A		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.1143+14680G>A		intron	N/A	ENSP00000492152.1
	ELP4	ENST00000395934.2	TSL:1	c.1143+14680G>A		intron	N/A	ENSP00000379267.2
	ELP4	ENST00000379163.10	TSL:2	c.1146+14680G>A		intron	N/A	ENSP00000368461.5

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92218 AN: 151860 Hom.: 31741 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.884

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.759

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.607 AC: 92217 AN: 151978 Hom.: 31735 Cov.: 32 AF XY: 0.613 AC XY: 45555 AN XY: 74282

African (AFR) AF: 0.261 AC: 10823 AN: 41410

American (AMR) AF: 0.605 AC: 9233 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2395 AN: 3466

East Asian (EAS) AF: 0.667 AC: 3437 AN: 5150

South Asian (SAS) AF: 0.656 AC: 3160 AN: 4814

European-Finnish (FIN) AF: 0.884 AC: 9365 AN: 10594

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.759 AC: 51617 AN: 67970

Other (OTH) AF: 0.600 AC: 1266 AN: 2110

Alfa AF: 0.643 Hom.: 5230

Bravo AF: 0.571

Asia WGS AF: 0.603 AC: 2095 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.83
DANN	Benign	0.64
PhyloP100		1.1
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: rs4922571; hg19: chr11-31686449;