NM_019040.5:c.1144-3397A>T

Variant names:

• chr11-31779996-A-T
• rs3026411
• NM_019040.5:c.1144-3397A>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.1144-3397A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,104 control chromosomes in the GnomAD database, including 6,878 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 0.28 (6878 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ELP4 NM_019040.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107
• Publications: 5 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.1144-3397A>T		intron_variant	Intron 9 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.1572-3397A>T		intron_variant	Intron 11 of 11		NP_001275655.1
ELP4	NM_001288725.2	c.1286-3397A>T		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.1144-3397A>T		intron_variant	Intron 9 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42370 AN: 151986 Hom.: 6880 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.0358

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.279 AC: 42373 AN: 152104 Hom.: 6878 Cov.: 32 AF XY: 0.277 AC XY: 20559 AN XY: 74350

African (AFR) AF: 0.135 AC: 5619 AN: 41518

American (AMR) AF: 0.277 AC: 4235 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1259 AN: 3470

East Asian (EAS) AF: 0.0359 AC: 186 AN: 5186

South Asian (SAS) AF: 0.219 AC: 1054 AN: 4806

European-Finnish (FIN) AF: 0.379 AC: 4006 AN: 10572

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24853 AN: 67956

Other (OTH) AF: 0.281 AC: 594 AN: 2114

Alfa AF: 0.313 Hom.: 976

Bravo AF: 0.267

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.59
PhyloP100		0.11
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: rs3026411; hg19: chr11-31801544;