11-31603826-C-A

Position:

• chr11-31603826-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_019040.5(ELP4):​c.572C>A​(p.Pro191Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00353 in 1,611,180 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (8 hom.)
• Consequence: ELP4 NM_019040.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.86

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008760184).
• BP6: Variant 11-31603826-C-A is Benign according to our data. Variant chr11-31603826-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 707203.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-31603826-C-A is described in Lovd as [Likely_benign].
• BS2: High AC in GnomAd4 at 387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELP4	NM_019040.5	c.572C>A	p.Pro191Gln	missense_variant	5/10	ENST00000640961.2	NP_061913.3
ELP4	NM_001288726.2	c.572C>A	p.Pro191Gln	missense_variant	5/12		NP_001275655.1
ELP4	NM_001288725.2	c.575C>A	p.Pro192Gln	missense_variant	5/11		NP_001275654.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELP4	ENST00000640961.2	c.572C>A	p.Pro191Gln	missense_variant	5/10	1	NM_019040.5	ENSP00000492152.1

Frequencies

GnomAD3 genomes AF: 0.00255 AC: 387 AN: 151682 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000797

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00450

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00264 AC: 655 AN: 248540 Hom.: 0 AF XY: 0.00254 AC XY: 343 AN XY: 134920

Gnomad AFR exome AF: 0.000971

Gnomad AMR exome AF: 0.00180

Gnomad ASJ exome AF: 0.000896

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000295

Gnomad FIN exome AF: 0.00186

Gnomad NFE exome AF: 0.00453

Gnomad OTH exome AF: 0.00166

GnomAD4 exome AF: 0.00363 AC: 5295 AN: 1459380 Hom.: 8 Cov.: 30 AF XY: 0.00362 AC XY: 2627 AN XY: 726038

Gnomad4 AFR exome AF: 0.000509

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.000692

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000337

Gnomad4 FIN exome AF: 0.00172

Gnomad4 NFE exome AF: 0.00442

Gnomad4 OTH exome AF: 0.00246

GnomAD4 genome AF: 0.00255 AC: 387 AN: 151800 Hom.: 2 Cov.: 32 AF XY: 0.00222 AC XY: 165 AN XY: 74170

Gnomad4 AFR AF: 0.000795

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00450

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00336 Hom.: 2

Bravo AF: 0.00230

TwinsUK AF: 0.00378 AC: 14

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.000552 AC: 2

ESP6500EA AF: 0.00332 AC: 27

ExAC AF: 0.00276 AC: 333

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 17, 2023	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	ELP4: BP4, BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

ELP4-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 20, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;.;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.92	D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.0088	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.18	.;.;N;.;.;.;.;.;.;.;.;N
REVEL	Benign	0.20
Sift	Benign	0.23	.;.;T;.;.;.;.;.;.;.;.;T
Sift4G	Benign	0.20	.;.;T;.;.;.;.;.;.;.;.;T
Polyphen		0.97	D;.;.;.;.;.;.;.;.;.;.;D
Vest4		0.38, 0.36
MVP		0.67
MPC		0.27
ClinPred		0.026	T
GERP RS		6.1
Varity_R		0.069
gMVP		0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs201699595; hg19: chr11-31625373;