Genetic Variant ENSG00000293259:n.114A>G (chr3-183885037-A-G) – 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.114A>G 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 0.146 in 982,496 control chromosomes in the GnomAD database, including 13,790 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 0.13 ( 1852 hom., cov: 33)

Exomes 𝑓: 0.15 ( 11938 hom. )

Consequence

ENSG00000293259
ENST00000445165.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.75

Publications

5 publications found

Variant links:

COSMIC-nc: COSV57699842

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:

Genome browser will be placed here

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=-1.03).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7 link	c.-191T>C		upstream_gene_variant		ENST00000317096.9	NP_061092.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9 link	c.-191T>C		upstream_gene_variant		1	NM_018622.7	ENSP00000325421.5
ENSG00000283765	ENST00000639401.1 link	c.-191T>C		upstream_gene_variant		5		ENSP00000491227.1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19687

AN:

151854

Hom.:

1838

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0410

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.0943

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.258

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.130

GnomAD4 exome

AF:

0.149

AC:

123965

AN:

830524

Hom.:

11938

Cov.:

AF XY:

0.152

AC XY:

63779

AN XY:

419834

show subpopulations

African (AFR)

AF:

0.0380

AC:

798

AN:

20990

American (AMR)

AF:

0.225

AC:

6528

AN:

28972

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

1820

AN:

18124

East Asian (EAS)

AF:

0.457

AC:

14915

AN:

32616

South Asian (SAS)

AF:

0.244

AC:

14557

AN:

59654

European-Finnish (FIN)

AF:

0.194

AC:

6020

AN:

30976

Middle Eastern (MID)

AF:

0.0969

AC:

271

AN:

2798

European-Non Finnish (NFE)

AF:

0.123

AC:

73214

AN:

597570

Other (OTH)

AF:

0.150

AC:

5842

AN:

38824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

4956

9911

14867

19822

24778

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2246

4492

6738

8984

11230

<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:

0.130

AC:

19714

AN:

151972

Hom.:

1852

Cov.:

AF XY:

0.137

AC XY:

10196

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.0411

AC:

1703

AN:

41478

American (AMR)

AF:

0.196

AC:

2993

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0943

AC:

327

AN:

3466

East Asian (EAS)

AF:

0.450

AC:

2307

AN:

5122

South Asian (SAS)

AF:

0.256

AC:

1232

AN:

4812

European-Finnish (FIN)

AF:

0.197

AC:

2084

AN:

10566

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8552

AN:

67958

Other (OTH)

AF:

0.139

AC:

292

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

857

1714

2570

3427

4284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<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:

0.113

Hom.:

151

Bravo

AF:

0.124

Asia WGS

AF:

0.360

AC:

1249

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.41

(source)

DANN

Benign

0.57

PhyloP100

-4.8

PromoterAI

-0.086

Neutral

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over