Genetic Variant NM_004764.5:c.1128G>A (chr12-130354620-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_004764.5(PIWIL1):c.1128G>A(p.Leu376Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,607,994 control chromosomes in the GnomAD database, including 28,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.19 ( 2786 hom., cov: 32)

Exomes 𝑓: 0.18 ( 25328 hom. )

Consequence

PIWIL1
NM_004764.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.0280

Publications

14 publications found

Variant links:

Genes affected

PIWIL1 (HGNC:9007): (piwi like RNA-mediated gene silencing 1) This gene encodes a member of the PIWI subfamily of Argonaute proteins, evolutionarily conserved proteins containing both PAZ and Piwi motifs that play important roles in stem cell self-renewal, RNA silencing, and translational regulation in diverse organisms. The encoded protein may play a role as an intrinsic regulator of the self-renewal capacity of germline and hematopoietic stem cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

PIWIL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 12-130354620-G-A is Benign according to our data. Variant chr12-130354620-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060640.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.028 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004764.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL1	NM_004764.5	MANE Select	c.1128G>A	p.Leu376Leu	synonymous	Exon 10 of 21	NP_004755.2	Q96J94-1
	PIWIL1	NM_001190971.2		c.1128G>A	p.Leu376Leu	synonymous	Exon 10 of 20	NP_001177900.1	Q96J94-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL1	ENST00000245255.7	TSL:1 MANE Select	c.1128G>A	p.Leu376Leu	synonymous	Exon 10 of 21	ENSP00000245255.3	Q96J94-1

Frequencies

GnomAD3 genomes

AF:

0.187

AC:

28383

AN:

151968

Hom.:

2771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.0954

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.204

GnomAD2 exomes

AF:

0.173

AC:

42317

AN:

244828

AF XY:

0.178

show subpopulations

Gnomad AFR exome

AF:

0.221

Gnomad AMR exome

AF:

0.0976

Gnomad ASJ exome

AF:

0.260

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.184

AC:

267733

AN:

1455908

Hom.:

25328

Cov.:

AF XY:

0.185

AC XY:

134125

AN XY:

724242

show subpopulations

African (AFR)

AF:

0.227

AC:

7491

AN:

33004

American (AMR)

AF:

0.105

AC:

4508

AN:

42928

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

6722

AN:

25776

East Asian (EAS)

AF:

0.105

AC:

4173

AN:

39662

South Asian (SAS)

AF:

0.217

AC:

18456

AN:

85112

European-Finnish (FIN)

AF:

0.143

AC:

7655

AN:

53360

Middle Eastern (MID)

AF:

0.213

AC:

1219

AN:

5710

European-Non Finnish (NFE)

AF:

0.186

AC:

206094

AN:

1110230

Other (OTH)

AF:

0.190

AC:

11415

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

10844

21687

32531

43374

54218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7364

14728

22092

29456

36820

<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:

0.187

AC:

28425

AN:

152086

Hom.:

2786

Cov.:

AF XY:

0.184

AC XY:

13703

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.217

AC:

9009

AN:

41488

American (AMR)

AF:

0.138

AC:

2107

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

896

AN:

3470

East Asian (EAS)

AF:

0.115

AC:

595

AN:

5166

South Asian (SAS)

AF:

0.212

AC:

1018

AN:

4800

European-Finnish (FIN)

AF:

0.151

AC:

1597

AN:

10578

Middle Eastern (MID)

AF:

0.245

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.185

AC:

12599

AN:

67980

Other (OTH)

AF:

0.211

AC:

445

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1167

2334

3500

4667

5834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.188

Hom.:

7720

Bravo

AF:

0.187

Asia WGS

AF:

0.216

AC:

750

AN:

3478

EpiCase

AF:

0.183

EpiControl

AF:

0.188

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

PIWIL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.1

(source)

DANN

Benign

0.69

PhyloP100

0.028

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over