Genetic Variant ENST00000445165.2:n.120C>G (chr3-183885043-C-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.120C>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 0.145 in 945,084 control chromosomes in the GnomAD database, including 13,430 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 ( 1844 hom., cov: 33)

Exomes 𝑓: 0.15 ( 11586 hom. )

Consequence

ENSG00000293259
ENST00000445165.2 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.25

Publications

4 publications found

Variant links:

COSMIC-nc: COSV57699844

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=-1.04).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PARL	NM_018622.7 link	c.-197G>C		upstream_gene_variant		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.-197G>C		upstream_gene_variant		1	NM_018622.7	ENSP00000325421.5		Q9H300-1
ENSG00000283765	ENST00000639401.1 link	c.-197G>C		upstream_gene_variant		5		ENSP00000491227.1		A0A1W2PP11

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19392

AN:

152066

Hom.:

1830

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0341

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.0926

Gnomad EAS

AF:

0.450

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.197

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.126

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.148

AC:

117593

AN:

792900

Hom.:

11586

Cov.:

AF XY:

0.151

AC XY:

60754

AN XY:

401532

show subpopulations

African (AFR)

AF:

0.0303

AC:

609

AN:

20104

American (AMR)

AF:

0.232

AC:

6464

AN:

27840

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

1752

AN:

17522

East Asian (EAS)

AF:

0.456

AC:

14805

AN:

32434

South Asian (SAS)

AF:

0.245

AC:

14251

AN:

58122

European-Finnish (FIN)

AF:

0.195

AC:

5980

AN:

30664

Middle Eastern (MID)

AF:

0.0990

AC:

266

AN:

2688

European-Non Finnish (NFE)

AF:

0.120

AC:

67859

AN:

565952

Other (OTH)

AF:

0.149

AC:

5607

AN:

37574

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4846

9691

14537

19382

24228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.128

AC:

19420

AN:

152184

Hom.:

1844

Cov.:

AF XY:

0.135

AC XY:

10050

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.0342

AC:

1420

AN:

41568

American (AMR)

AF:

0.195

AC:

2984

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0926

AC:

321

AN:

3466

East Asian (EAS)

AF:

0.451

AC:

2312

AN:

5128

South Asian (SAS)

AF:

0.255

AC:

1232

AN:

4824

European-Finnish (FIN)

AF:

0.197

AC:

2086

AN:

10596

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.126

AC:

8549

AN:

67998

Other (OTH)

AF:

0.137

AC:

290

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

853

1706

2559

3412

4265

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.118

Hom.:

155

Bravo

AF:

0.122

Asia WGS

AF:

0.359

AC:

1247

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

0.52

(source)

DANN

Benign

0.49

PhyloP100

-2.3

PromoterAI

0.081

Neutral

(source)

Splicing

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

Publications

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ENST00000445165.2:n.120C>G

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