chr12-130367629-G-T

Position:

• chr12-130367629-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004764.5(PIWIL1):​c.2321+371G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0539 in 152,280 control chromosomes in the GnomAD database, including 589 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 0.054 (589 hom., cov: 33)
• Consequence: PIWIL1 NM_004764.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIWIL1	NM_004764.5	c.2321+371G>T		intron_variant		ENST00000245255.7	NP_004755.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIWIL1	ENST00000245255.7	c.2321+371G>T		intron_variant		1	NM_004764.5	ENSP00000245255.3
PIWIL1	ENST00000541480.1	n.337+371G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0538 AC: 8192 AN: 152162 Hom.: 589 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0995

Gnomad ASJ AF: 0.0517

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0422

Gnomad OTH AF: 0.0626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0539 AC: 8201 AN: 152280 Hom.: 589 Cov.: 33 AF XY: 0.0565 AC XY: 4210 AN XY: 74460

Gnomad4 AFR AF: 0.0132

Gnomad4 AMR AF: 0.0998

Gnomad4 ASJ AF: 0.0517

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.0858

Gnomad4 FIN AF: 0.0407

Gnomad4 NFE AF: 0.0422

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0303 Hom.: 28

Bravo AF: 0.0569

Asia WGS AF: 0.206 AC: 717 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs11060845; hg19: chr12-130852174;