NM_019040.5:c.338T>C

Variant names:

• chr11-31539740-T-C
• rs201333718
• NM_019040.5:c.338T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_019040.5(ELP4):​c.338T>C​(p.Leu113Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0046 in 1,612,314 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0047 (34 hom.)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.34
• Publications: 7 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011266887).
• BP6: Variant 11-31539740-T-C is Benign according to our data. Variant chr11-31539740-T-C is described in ClinVar as Benign. ClinVar VariationId is 772330.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 535 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.338T>C	p.Leu113Ser	missense	Exon 3 of 10	NP_061913.3
	ELP4	NM_001288726.2		c.338T>C	p.Leu113Ser	missense	Exon 3 of 12	NP_001275655.1	G5E9D4
	ELP4	NM_001288725.2		c.338T>C	p.Leu113Ser	missense	Exon 3 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.338T>C	p.Leu113Ser	missense	Exon 3 of 10	ENSP00000492152.1	Q96EB1-1
	ELP4	ENST00000395934.2	TSL:1	c.338T>C	p.Leu113Ser	missense	Exon 3 of 12	ENSP00000379267.2	G5E9D4
	ELP4	ENST00000379163.10	TSL:2	c.338T>C	p.Leu113Ser	missense	Exon 3 of 11	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes AF: 0.00351 AC: 535 AN: 152216 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000651

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00223

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00514

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00476 AC: 1181 AN: 248216 AF XY: 0.00530

Gnomad AFR exome AF: 0.000647

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00144

Gnomad NFE exome AF: 0.00477

Gnomad OTH exome AF: 0.00367

GnomAD4 exome AF: 0.00471 AC: 6876 AN: 1459980 Hom.: 34 Cov.: 30 AF XY: 0.00509 AC XY: 3696 AN XY: 726192

African (AFR) AF: 0.000658 AC: 22 AN: 33454

American (AMR) AF: 0.00222 AC: 99 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.00464 AC: 121 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39606

South Asian (SAS) AF: 0.0146 AC: 1249 AN: 85662

European-Finnish (FIN) AF: 0.00208 AC: 111 AN: 53374

Middle Eastern (MID) AF: 0.00781 AC: 45 AN: 5762

European-Non Finnish (NFE) AF: 0.00440 AC: 4888 AN: 1111136

Other (OTH) AF: 0.00565 AC: 341 AN: 60334

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152334 Hom.: 2 Cov.: 33 AF XY: 0.00357 AC XY: 266 AN XY: 74500

African (AFR) AF: 0.000649 AC: 27 AN: 41584

American (AMR) AF: 0.00222 AC: 34 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00720 AC: 25 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4826

European-Finnish (FIN) AF: 0.00198 AC: 21 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00516 AC: 351 AN: 68024

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00427 Hom.: 11

Bravo AF: 0.00295

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000275 AC: 1

ESP6500EA AF: 0.00405 AC: 33

ExAC AF: 0.00498 AC: 602

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		4.3
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.79	P
Vest4		0.72
MVP		0.76
MPC		0.15
ClinPred		0.046	T
GERP RS		4.2
Varity_R		0.55
gMVP		0.89
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs201333718; hg19: chr11-31561287; COSMIC: COSV99052342;