Genetic Variant ENSG00000293259:n.232C>T (chr3-183885155-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000445165.2(ENSG00000293259):n.232C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 531,368 control chromosomes in the GnomAD database, including 54,328 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 0.42 ( 13830 hom., cov: 32)

Exomes 𝑓: 0.46 ( 40498 hom. )

Consequence

ENSG00000293259
ENST00000445165.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.535

Publications

10 publications found

Variant links:

COSMIC-nc: COSV57700275

Genes affected

ENSG00000293259 (HGNC:):

ENSG00000293259 links:

PARL (HGNC:18253): (presenilin associated rhomboid like) This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]

PARL links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
ENSG00000293259	ENST00000445165.2 link	n.232C>T	non_coding_transcript_exon_variant	Exon 1 of 2	2
ENSG00000293259	ENST00000833400.1 link	n.119C>T	non_coding_transcript_exon_variant	Exon 1 of 2
PARL	ENST00000639100.1 link	c.-841G>A	upstream_gene_variant		5	ENSP00000491186.1	A0A1W2PP66

Frequencies

GnomAD3 genomes

AF:

0.419

AC:

63699

AN:

151948

Hom.:

13828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.554

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.418

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.452

GnomAD4 exome

AF:

0.458

AC:

173671

AN:

379302

Hom.:

40498

Cov.:

AF XY:

0.457

AC XY:

91004

AN XY:

199040

show subpopulations

African (AFR)

AF:

0.333

AC:

3656

AN:

10974

American (AMR)

AF:

0.506

AC:

8298

AN:

16390

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

6370

AN:

11744

East Asian (EAS)

AF:

0.456

AC:

11380

AN:

24972

South Asian (SAS)

AF:

0.420

AC:

18877

AN:

44938

European-Finnish (FIN)

AF:

0.328

AC:

7544

AN:

23024

Middle Eastern (MID)

AF:

0.555

AC:

902

AN:

1624

European-Non Finnish (NFE)

AF:

0.477

AC:

106661

AN:

223746

Other (OTH)

AF:

0.456

AC:

9983

AN:

21890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

4874

9748

14621

19495

24369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

574

1148

1722

2296

2870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.419

AC:

63723

AN:

152066

Hom.:

13830

Cov.:

AF XY:

0.412

AC XY:

30642

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.326

AC:

13517

AN:

41472

American (AMR)

AF:

0.480

AC:

7337

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.554

AC:

1922

AN:

3470

East Asian (EAS)

AF:

0.423

AC:

2181

AN:

5162

South Asian (SAS)

AF:

0.418

AC:

2017

AN:

4822

European-Finnish (FIN)

AF:

0.289

AC:

3061

AN:

10580

Middle Eastern (MID)

AF:

0.548

AC:

161

AN:

294

European-Non Finnish (NFE)

AF:

0.475

AC:

32306

AN:

67964

Other (OTH)

AF:

0.448

AC:

948

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1919

3838

5757

7676

9595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

596

1192

1788

2384

2980

<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:

0.446

Hom.:

2546

Bravo

AF:

0.435

Asia WGS

AF:

0.416

AC:

1449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

6.0

(source)

DANN

Benign

0.74

PhyloP100

-0.54

PromoterAI

0.025

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over