dbSNP rs2276201: PACRG:c.156+74T>C (chr6-162728465-T-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_001080379.2(PACRG):c.156+74T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,551,346 control chromosomes in the GnomAD database, including 80,048 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 0.40 ( 15141 hom., cov: 31)

Exomes 𝑓: 0.29 ( 64907 hom. )

Consequence

PACRG
NM_001080379.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.601

Publications

14 publications found

Variant links:

Genes affected

PACRG (HGNC:19152): (parkin coregulated) This gene encodes a protein that is conserved across metazoans. In vertebrates, this gene is linked in a head-to-head arrangement with the adjacent parkin gene, which is associated with autosomal recessive juvenile Parkinson's disease. These genes are co-regulated in various tissues and they share a bi-directional promoter. Both genes are associated with susceptibility to leprosy. The parkin co-regulated gene protein forms a large molecular complex with chaperones, including heat shock proteins 70 and 90, and chaperonin components. This protein is also a component of Lewy bodies in Parkinson's disease patients, and it suppresses unfolded Pael receptor-induced neuronal cell death. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

PACRG 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=-0.78).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PACRG	NM_001080379.2 link	c.156+74T>C		intron_variant	Intron 1 of 4	ENST00000366888.7	NP_001073848.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PACRG	ENST00000366888.7 link	c.156+74T>C		intron_variant	Intron 1 of 4	1	NM_001080379.2	ENSP00000355854.2		Q96M98-2

Frequencies

GnomAD3 genomes

AF:

0.404

AC:

61390

AN:

151778

Hom.:

15122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.693

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.465

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.293

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.404

Gnomad NFE

AF:

0.276

Gnomad OTH

AF:

0.391

GnomAD4 exome

AF:

0.294

AC:

411451

AN:

1399450

Hom.:

64907

AF XY:

0.293

AC XY:

203093

AN XY:

693576

show subpopulations

African (AFR)

AF:

0.710

AC:

23102

AN:

32532

American (AMR)

AF:

0.476

AC:

20266

AN:

42534

Ashkenazi Jewish (ASJ)

AF:

0.319

AC:

7721

AN:

24176

East Asian (EAS)

AF:

0.197

AC:

7726

AN:

39176

South Asian (SAS)

AF:

0.301

AC:

24387

AN:

80994

European-Finnish (FIN)

AF:

0.223

AC:

8642

AN:

38742

Middle Eastern (MID)

AF:

0.348

AC:

1928

AN:

5546

European-Non Finnish (NFE)

AF:

0.278

AC:

299019

AN:

1077354

Other (OTH)

AF:

0.320

AC:

18660

AN:

58396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

13984

27968

41952

55936

69920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10284

20568

30852

41136

51420

<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:

0.405

AC:

61444

AN:

151896

Hom.:

15141

Cov.:

AF XY:

0.400

AC XY:

29670

AN XY:

74238

show subpopulations

African (AFR)

AF:

0.693

AC:

28654

AN:

41370

American (AMR)

AF:

0.465

AC:

7094

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1120

AN:

3464

East Asian (EAS)

AF:

0.198

AC:

1019

AN:

5146

South Asian (SAS)

AF:

0.292

AC:

1403

AN:

4812

European-Finnish (FIN)

AF:

0.204

AC:

2160

AN:

10584

Middle Eastern (MID)

AF:

0.407

AC:

118

AN:

290

European-Non Finnish (NFE)

AF:

0.276

AC:

18765

AN:

67942

Other (OTH)

AF:

0.391

AC:

824

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1603

3206

4808

6411

8014

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.322

Hom.:

33909

Bravo

AF:

0.436

Asia WGS

AF:

0.310

AC:

1080

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.1

(source)

DANN

Benign

0.64

PhyloP100

-0.60

PromoterAI

-0.0054

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over