Genetic Variant PIWIL1:c.191-4delT (chr12-130345740-AT-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_004764.5(PIWIL1):c.191-4delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00232 in 1,563,730 control chromosomes in the GnomAD database, including 45 homozygotes. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.0026 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 39 hom. )

Consequence

PIWIL1
NM_004764.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.23

Publications

2 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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00255 (387/151530) while in subpopulation SAS AF = 0.0191 (91/4766). AF 95% confidence interval is 0.0159. There are 6 homozygotes in GnomAd4. There are 266 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

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.191-4delT		splice_region intron	N/A	NP_004755.2	Q96J94-1
	PIWIL1	NM_001190971.2		c.191-4delT		splice_region intron	N/A	NP_001177900.1	Q96J94-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PIWIL1	ENST00000245255.7	TSL:1 MANE Select	c.191-4delT	splice_region intron	N/A	ENSP00000245255.3	Q96J94-1
PIWIL1	ENST00000542723.1	TSL:2	c.191-4delT	splice_region intron	N/A	ENSP00000438582.1	F5H2F7
PIWIL1	ENST00000546060.5	TSL:4	c.191-4delT	splice_region intron	N/A	ENSP00000442086.1	F5H889

Frequencies

GnomAD3 genomes

AF:

0.00254

AC:

384

AN:

151420

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000510

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000264

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00618

Gnomad SAS

AF:

0.0191

Gnomad FIN

AF:

0.0152

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00102

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.00496

AC:

1095

AN:

220652

AF XY:

0.00559

show subpopulations

Gnomad AFR exome

AF:

0.000741

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00323

Gnomad EAS exome

AF:

0.00349

Gnomad FIN exome

AF:

0.0177

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00594

GnomAD4 exome

AF:

0.00230

AC:

3247

AN:

1412200

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

1910

AN XY:

702718

show subpopulations

African (AFR)

AF:

0.000589

AC:

AN:

32240

American (AMR)

AF:

0.000254

AC:

AN:

43312

Ashkenazi Jewish (ASJ)

AF:

0.00239

AC:

AN:

25064

East Asian (EAS)

AF:

0.00250

AC:

AN:

38020

South Asian (SAS)

AF:

0.0158

AC:

1313

AN:

83300

European-Finnish (FIN)

AF:

0.0182

AC:

945

AN:

51840

Middle Eastern (MID)

AF:

0.00302

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.000558

AC:

600

AN:

1074576

Other (OTH)

AF:

0.00321

AC:

187

AN:

58220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

165

331

496

662

827

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00255

AC:

387

AN:

151530

Hom.:

Cov.:

AF XY:

0.00359

AC XY:

266

AN XY:

74034

show subpopulations

African (AFR)

AF:

0.000557

AC:

AN:

41322

American (AMR)

AF:

0.000263

AC:

AN:

15190

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3460

East Asian (EAS)

AF:

0.00639

AC:

AN:

5168

South Asian (SAS)

AF:

0.0191

AC:

AN:

4766

European-Finnish (FIN)

AF:

0.0152

AC:

159

AN:

10444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00102

AC:

AN:

67878

Other (OTH)

AF:

0.000476

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00250

Hom.:

Bravo

AF:

0.000805

Asia WGS

AF:

0.0160

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.22

Position offset: 21

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