rs1232180

Variant names:

• chr11-31618864-G-A
• rs1232180
• NM_019040.5:c.654-8246G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-31618864-G-A
• chr11-31618864-G-T

Variant summary

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

The NM_019040.5(ELP4):​c.654-8246G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,924 control chromosomes in the GnomAD database, including 4,796 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 0.24 (4796 hom., cov: 31)
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.654-8246G>A		intron_variant	Intron 5 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.654-8246G>A		intron_variant	Intron 5 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.657-8246G>A		intron_variant	Intron 5 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.654-8246G>A		intron_variant	Intron 5 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35956 AN: 151806 Hom.: 4796 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.237 AC: 35955 AN: 151924 Hom.: 4796 Cov.: 31 AF XY: 0.235 AC XY: 17422 AN XY: 74236

African (AFR) AF: 0.129 AC: 5345 AN: 41466

American (AMR) AF: 0.238 AC: 3630 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3470

East Asian (EAS) AF: 0.0372 AC: 192 AN: 5156

South Asian (SAS) AF: 0.203 AC: 977 AN: 4820

European-Finnish (FIN) AF: 0.301 AC: 3171 AN: 10546

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20523 AN: 67918

Other (OTH) AF: 0.231 AC: 488 AN: 2114

Alfa AF: 0.148 Hom.: 312

Bravo AF: 0.227

Asia WGS AF: 0.109 AC: 379 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.71
DANN	Benign	0.43
PhyloP100		-0.60
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: rs1232180; hg19: chr11-31640411;