rs374456201

Variant names:

• chr12-130345740-AT-A
• rs374456201
• NM_004764.5:c.191-4delT

Your query was ambiguous. Multiple possible variants found:

• chr12-130345740-AT-A
• chr12-130345740-AT-ATT
• chr12-130345740-AT-ATTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0026 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0023 (39 hom.)
• Consequence: PIWIL1 NM_004764.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIWIL1	NM_004764.5	c.191-4delT		splice_region_variant, intron_variant	Intron 3 of 20	ENST00000245255.7	NP_004755.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIWIL1	ENST00000245255.7	c.191-4delT		splice_region_variant, intron_variant	Intron 3 of 20	1	NM_004764.5	ENSP00000245255.3

Frequencies

GnomAD3 genomes AF: 0.00254 AC: 384 AN: 151420 Hom.: 6 Cov.: 33

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

GnomAD3 exomes AF: 0.00496 AC: 1095 AN: 220652 Hom.: 8 AF XY: 0.00559 AC XY: 667 AN XY: 119226

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 SAS exome AF: 0.0189

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.: 39 Cov.: 30 AF XY: 0.00272 AC XY: 1910 AN XY: 702718

Gnomad4 AFR exome AF: 0.000589

Gnomad4 AMR exome AF: 0.000254

Gnomad4 ASJ exome AF: 0.00239

Gnomad4 EAS exome AF: 0.00250

Gnomad4 SAS exome AF: 0.0158

Gnomad4 FIN exome AF: 0.0182

Gnomad4 NFE exome AF: 0.000558

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.00255 AC: 387 AN: 151530 Hom.: 6 Cov.: 33 AF XY: 0.00359 AC XY: 266 AN XY: 74034

Gnomad4 AFR AF: 0.000557

Gnomad4 AMR AF: 0.000263

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00639

Gnomad4 SAS AF: 0.0191

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.00102

Gnomad4 OTH AF: 0.000476

Alfa AF: 0.00250 Hom.: 0

Bravo AF: 0.000805

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs374456201; hg19: chr12-130830285;