dbSNP rs10488688: ELP4:c.1144-15827G>C (chr11-31767566-G-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_019040.5(ELP4):c.1144-15827G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 151,854 control chromosomes in the GnomAD database, including 4,503 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 0.23 ( 4503 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

ELP4
NM_019040.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0120

Publications

0 publications found

Variant links:

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)

ELP4 links:

ELP4-AS1 (HGNC:58222):

ELP4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ELP4	NM_019040.5	MANE Select	c.1144-15827G>C	intron	N/A	NP_061913.3
ELP4	NM_001288726.2		c.1571+4017G>C	intron	N/A	NP_001275655.1	G5E9D4
ELP4	NM_001288725.2		c.1285+4017G>C	intron	N/A	NP_001275654.1	Q96EB1-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ELP4	ENST00000640961.2	TSL:1 MANE Select	c.1144-15827G>C	intron	N/A	ENSP00000492152.1	Q96EB1-1
ELP4	ENST00000395934.2	TSL:1	c.1571+4017G>C	intron	N/A	ENSP00000379267.2	G5E9D4
ELP4	ENST00000379163.10	TSL:2	c.1285+4017G>C	intron	N/A	ENSP00000368461.5	Q96EB1-3

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34918

AN:

151738

Hom.:

4502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.520

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.0372

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.225

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.230

AC:

34918

AN:

151854

Hom.:

4503

Cov.:

AF XY:

0.228

AC XY:

16945

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.129

AC:

5333

AN:

41398

American (AMR)

AF:

0.232

AC:

3529

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

1047

AN:

3466

East Asian (EAS)

AF:

0.0373

AC:

193

AN:

5178

South Asian (SAS)

AF:

0.203

AC:

981

AN:

4824

European-Finnish (FIN)

AF:

0.288

AC:

3033

AN:

10530

Middle Eastern (MID)

AF:

0.271

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19784

AN:

67906

Other (OTH)

AF:

0.221

AC:

465

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1320

2641

3961

5282

6602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.253

Hom.:

634

Bravo

AF:

0.221

Asia WGS

AF:

0.107

AC:

373

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

-0.012

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over