rs10767903

Variant names:

• chr11-31681804-C-T
• rs10767903
• ENST00000395934.2:c.1161C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000395934.2(ELP4):​c.1161C>T​(p.His387His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 186,394 control chromosomes in the GnomAD database, including 41,836 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 (31420 hom., cov: 25)
  • Exomes 𝑓: 0.74 (10416 hom.)
• Consequence: ELP4 ENST00000395934.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 4 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.07).
• BP7: Synonymous conserved (PhyloP=-0.969 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELP4	NM_019040.5	c.1143+31583C>T		intron_variant	Intron 9 of 9	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.1161C>T	p.His387His	synonymous_variant	Exon 10 of 12		NP_001275655.1
ELP4	NM_001288725.2	c.1146+31583C>T		intron_variant	Intron 9 of 10		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.1143+31583C>T		intron_variant	Intron 9 of 9	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.609 AC: 91168 AN: 149728 Hom.: 31428 Cov.: 25

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.886

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.610

GnomAD2 exomes AF: 0.663 AC: 988 AN: 1490 AF XY: 0.671

Gnomad AFR exome AF: 0.183

Gnomad AMR exome AF: 0.641

Gnomad ASJ exome AF: 0.776

Gnomad EAS exome AF: 0.736

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.740

Gnomad OTH exome AF: 0.565

GnomAD4 exome AF: 0.742 AC: 27119 AN: 36560 Hom.: 10416 Cov.: 0 AF XY: 0.730 AC XY: 15345 AN XY: 21010

African (AFR) AF: 0.270 AC: 75 AN: 278

American (AMR) AF: 0.629 AC: 521 AN: 828

Ashkenazi Jewish (ASJ) AF: 0.687 AC: 569 AN: 828

East Asian (EAS) AF: 0.677 AC: 172 AN: 254

South Asian (SAS) AF: 0.670 AC: 6346 AN: 9476

European-Finnish (FIN) AF: 0.873 AC: 2535 AN: 2904

Middle Eastern (MID) AF: 0.741 AC: 80 AN: 108

European-Non Finnish (NFE) AF: 0.772 AC: 15566 AN: 20172

Other (OTH) AF: 0.733 AC: 1255 AN: 1712

GnomAD4 genome AF: 0.608 AC: 91160 AN: 149834 Hom.: 31420 Cov.: 25 AF XY: 0.614 AC XY: 44865 AN XY: 73030

African (AFR) AF: 0.262 AC: 10599 AN: 40486

American (AMR) AF: 0.606 AC: 9106 AN: 15024

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2385 AN: 3458

East Asian (EAS) AF: 0.670 AC: 3383 AN: 5046

South Asian (SAS) AF: 0.657 AC: 3089 AN: 4700

European-Finnish (FIN) AF: 0.886 AC: 9057 AN: 10226

Middle Eastern (MID) AF: 0.692 AC: 198 AN: 286

European-Non Finnish (NFE) AF: 0.760 AC: 51381 AN: 67622

Other (OTH) AF: 0.601 AC: 1251 AN: 2080

Alfa AF: 0.655 Hom.: 4615

Bravo AF: 0.571

Asia WGS AF: 0.602 AC: 2096 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.38
DANN	Benign	0.69
PhyloP100		-0.97
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: rs10767903; hg19: chr11-31703352; COSMIC: COSV63349281;