chr11-31541471-A-G

Variant names:

• chr11-31541471-A-G
• rs2973127
• NM_019040.5:c.381+1688A>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.381+1688A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,106 control chromosomes in the GnomAD database, including 12,158 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 0.36 (12158 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.381+1688A>G		intron_variant	Intron 3 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.381+1688A>G		intron_variant	Intron 3 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.381+1688A>G		intron_variant	Intron 3 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.381+1688A>G		intron_variant	Intron 3 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54659 AN: 151988 Hom.: 12106 Cov.: 32

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.330

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.367

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.360 AC: 54774 AN: 152106 Hom.: 12158 Cov.: 32 AF XY: 0.354 AC XY: 26338 AN XY: 74382

African (AFR) AF: 0.625 AC: 25902 AN: 41466

American (AMR) AF: 0.382 AC: 5839 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.309 AC: 1072 AN: 3468

East Asian (EAS) AF: 0.330 AC: 1708 AN: 5168

South Asian (SAS) AF: 0.342 AC: 1647 AN: 4820

European-Finnish (FIN) AF: 0.117 AC: 1237 AN: 10608

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16293 AN: 67992

Other (OTH) AF: 0.376 AC: 792 AN: 2108

Alfa AF: 0.295 Hom.: 2703

Bravo AF: 0.391

Asia WGS AF: 0.388 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	13
DANN	Benign	0.64
PhyloP100		2.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2973127; hg19: chr11-31563018;