11-31594897-T-C

Variant names:

• chr11-31594897-T-C
• rs1024940919
• NM_019040.5:c.509T>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_019040.5(ELP4):​c.509T>C​(p.Met170Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000499 in 1,401,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.12
• Publications: 0 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
• ocular dysgenesis caused by defects in PAX6 regulation

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• aniridia 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3066706).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019040.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	NM_019040.5	MANE Select	c.509T>C	p.Met170Thr	missense	Exon 4 of 10	NP_061913.3
	ELP4	NM_001288726.2		c.509T>C	p.Met170Thr	missense	Exon 4 of 12	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.509T>C	p.Met170Thr	missense	Exon 4 of 11	NP_001275654.1	Q96EB1-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP4	ENST00000640961.2	TSL:1 MANE Select	c.509T>C	p.Met170Thr	missense	Exon 4 of 10	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.509T>C	p.Met170Thr	missense	Exon 4 of 12	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.509T>C	p.Met170Thr	missense	Exon 4 of 11	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000511 AC: 1 AN: 195762 AF XY: 0.00000927

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000103

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000499 AC: 7 AN: 1401588 Hom.: 0 Cov.: 30 AF XY: 0.00000431 AC XY: 3 AN XY: 695732

African (AFR) AF: 0.00 AC: 0 AN: 29640

American (AMR) AF: 0.00 AC: 0 AN: 29126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24552

East Asian (EAS) AF: 0.00 AC: 0 AN: 36708

South Asian (SAS) AF: 0.00 AC: 0 AN: 73000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00000641 AC: 7 AN: 1092126

Other (OTH) AF: 0.00 AC: 0 AN: 57888

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.020	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.1
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.16
Sift	Benign	0.14	T
Sift4G	Benign	0.18	T
Polyphen		0.48	P
Vest4		0.41
MutPred		0.62		Gain of methylation at K169 (P = 0.0284)
MVP		0.57
MPC		0.12
ClinPred		0.55	D
GERP RS		5.1
Varity_R		0.35
gMVP		0.37
Mutation Taster		=56/44	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1024940919; hg19: chr11-31616444;