Genetic Variant NM_001080379.2: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:

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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=-0.78).

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

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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