11-31778325-G-C

Variant names:

• chr11-31778325-G-C
• rs7125966
• NM_019040.5:c.1144-5068G>C

Variant summary

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

The NM_019040.5(ELP4):​c.1144-5068G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.696 in 152,088 control chromosomes in the GnomAD database, including 37,832 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 0.70 (37832 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• 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)

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 (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.1144-5068G>C		intron_variant	Intron 9 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.1572-5068G>C		intron_variant	Intron 11 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.1286-5068G>C		intron_variant	Intron 10 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.1144-5068G>C		intron_variant	Intron 9 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105733 AN: 151970 Hom.: 37771 Cov.: 31

Gnomad AFR AF: 0.867

Gnomad AMI AF: 0.796

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.546

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.696 AC: 105856 AN: 152088 Hom.: 37832 Cov.: 31 AF XY: 0.688 AC XY: 51170 AN XY: 74346

African (AFR) AF: 0.867 AC: 35998 AN: 41528

American (AMR) AF: 0.611 AC: 9336 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.717 AC: 2489 AN: 3472

East Asian (EAS) AF: 0.446 AC: 2296 AN: 5150

South Asian (SAS) AF: 0.684 AC: 3290 AN: 4812

European-Finnish (FIN) AF: 0.546 AC: 5771 AN: 10574

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44249 AN: 67964

Other (OTH) AF: 0.712 AC: 1500 AN: 2108

Alfa AF: 0.675 Hom.: 4422

Bravo AF: 0.704

Asia WGS AF: 0.582 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.54
PhyloP100		0.33
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: rs7125966; hg19: chr11-31799873;