rs7963072

Variant names:

• chr12-130344170-G-A
• rs7963072
• NM_004764.5:c.190+1069G>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.190+1069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 152,074 control chromosomes in the GnomAD database, including 4,004 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 0.22 (4004 hom., cov: 32)
• Consequence: PIWIL1 NM_004764.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 5 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL1	NM_004764.5	MANE Select	c.190+1069G>A		intron	N/A	NP_004755.2
	PIWIL1	NM_001190971.2		c.190+1069G>A		intron	N/A	NP_001177900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL1	ENST00000245255.7	TSL:1 MANE Select	c.190+1069G>A		intron	N/A	ENSP00000245255.3
	PIWIL1	ENST00000542723.1	TSL:2	c.190+1069G>A		intron	N/A	ENSP00000438582.1
	PIWIL1	ENST00000546060.5	TSL:4	c.190+1069G>A		intron	N/A	ENSP00000442086.1

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33029 AN: 151956 Hom.: 3988 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.218 AC: 33081 AN: 152074 Hom.: 4004 Cov.: 32 AF XY: 0.215 AC XY: 15991 AN XY: 74326

African (AFR) AF: 0.314 AC: 13043 AN: 41476

American (AMR) AF: 0.150 AC: 2292 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.122 AC: 630 AN: 5168

South Asian (SAS) AF: 0.235 AC: 1128 AN: 4810

European-Finnish (FIN) AF: 0.167 AC: 1757 AN: 10552

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12685 AN: 67990

Other (OTH) AF: 0.230 AC: 486 AN: 2110

Alfa AF: 0.196 Hom.: 1711

Bravo AF: 0.218

Asia WGS AF: 0.242 AC: 840 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.0
DANN	Benign	0.40
PhyloP100		0.12
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: rs7963072; hg19: chr12-130828715;