dbSNP rs2305666: PARL:c.829-120T>G (chr3-183833945-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018622.7(PARL):c.829-120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 731,038 control chromosomes in the GnomAD database, including 14,470 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 0.19 ( 3014 hom., cov: 32)

Exomes 𝑓: 0.19 ( 11456 hom. )

Consequence

PARL
NM_018622.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.669

Publications

8 publications found

Variant links:

Genes affected

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:

ENSG00000283765 (HGNC:):

ENSG00000283765 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7 link	c.829-120T>G		intron_variant	Intron 7 of 9	ENST00000317096.9	NP_061092.3	Q9H300-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PARL	ENST00000317096.9 link	c.829-120T>G		intron_variant	Intron 7 of 9	1	NM_018622.7	ENSP00000325421.5		Q9H300-1
ENSG00000283765	ENST00000639401.1 link	c.829-120T>G		intron_variant	Intron 7 of 10	5		ENSP00000491227.1		A0A1W2PP11

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29159

AN:

152098

Hom.:

2993

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.172

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.186

GnomAD4 exome

AF:

0.187

AC:

107980

AN:

578822

Hom.:

11456

AF XY:

0.184

AC XY:

57309

AN XY:

311590

show subpopulations

African (AFR)

AF:

0.197

AC:

3177

AN:

16142

American (AMR)

AF:

0.246

AC:

8492

AN:

34526

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

3844

AN:

19628

East Asian (EAS)

AF:

0.420

AC:

13753

AN:

32782

South Asian (SAS)

AF:

0.155

AC:

9644

AN:

62404

European-Finnish (FIN)

AF:

0.161

AC:

7907

AN:

48970

Middle Eastern (MID)

AF:

0.160

AC:

610

AN:

3812

European-Non Finnish (NFE)

AF:

0.165

AC:

54490

AN:

329610

Other (OTH)

AF:

0.196

AC:

6063

AN:

30948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

4599

9199

13798

18398

22997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.192

AC:

29216

AN:

152216

Hom.:

3014

Cov.:

AF XY:

0.191

AC XY:

14219

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.195

AC:

8091

AN:

41540

American (AMR)

AF:

0.236

AC:

3608

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

696

AN:

3472

East Asian (EAS)

AF:

0.429

AC:

2214

AN:

5166

South Asian (SAS)

AF:

0.153

AC:

739

AN:

4824

European-Finnish (FIN)

AF:

0.172

AC:

1823

AN:

10598

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11361

AN:

67996

Other (OTH)

AF:

0.193

AC:

407

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1229

2459

3688

4918

6147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.184

Hom.:

1375

Bravo

AF:

0.198

Asia WGS

AF:

0.304

AC:

1056

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.7

(source)

DANN

Benign

0.67

PhyloP100

0.67

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

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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