rs4759659

Variant names:

• chr12-130352743-G-A
• rs4759659
• NM_004764.5:c.1045-1794G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004764.5(PIWIL1):​c.1045-1794G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,022 control chromosomes in the GnomAD database, including 10,306 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 0.34 (10306 hom., cov: 32)
• Consequence: PIWIL1 NM_004764.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 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.1045-1794G>A		intron	N/A	NP_004755.2	Q96J94-1
	PIWIL1	NM_001190971.2		c.1045-1794G>A		intron	N/A	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.1045-1794G>A		intron	N/A	ENSP00000245255.3	Q96J94-1

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51969 AN: 151904 Hom.: 10304 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.342 AC: 51969 AN: 152022 Hom.: 10306 Cov.: 32 AF XY: 0.340 AC XY: 25272 AN XY: 74302

African (AFR) AF: 0.151 AC: 6250 AN: 41494

American (AMR) AF: 0.328 AC: 5014 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1681 AN: 3470

East Asian (EAS) AF: 0.152 AC: 787 AN: 5162

South Asian (SAS) AF: 0.267 AC: 1283 AN: 4810

European-Finnish (FIN) AF: 0.482 AC: 5084 AN: 10556

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30670 AN: 67944

Other (OTH) AF: 0.354 AC: 749 AN: 2116

Alfa AF: 0.423 Hom.: 15135

Bravo AF: 0.323

Asia WGS AF: 0.210 AC: 731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.51
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4759659; hg19: chr12-130837288;