rs2212361

Positions:

• chr11-94579157-T-C

Variant summary

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

The NM_152431.3(PIWIL4):​c.513+1665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,222 control chromosomes in the GnomAD database, including 4,353 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 0.23 (4353 hom., cov: 33)
• Consequence: PIWIL4 NM_152431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

Genes affected

PIWIL4 (HGNC:18444): (piwi like RNA-mediated gene silencing 4) PIWIL4 belongs to the Argonaute family of proteins, which function in development and maintenance of germline stem cells (Sasaki et al., 2003 [PubMed 12906857]).[supplied by OMIM, Mar 2008]

PIWIL4-AS1 (HGNC:55493): (PIWIL4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIWIL4	NM_152431.3	c.513+1665T>C		intron_variant		ENST00000299001.11
PIWIL4-AS1	NR_135093.1	n.524-33311A>G		intron_variant, non_coding_transcript_variant
PIWIL4-AS1	NR_135094.1	n.437-32832A>G		intron_variant, non_coding_transcript_variant
PIWIL4-AS1	NR_135096.1	n.623-3217A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIWIL4	ENST00000299001.11	c.513+1665T>C		intron_variant		1	NM_152431.3	P1
PIWIL4-AS1	ENST00000536540.5	n.438-33311A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34836 AN: 152104 Hom.: 4347 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.233

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

GnomAD4 genome AF: 0.229 AC: 34853 AN: 152222 Hom.: 4353 Cov.: 33 AF XY: 0.230 AC XY: 17111 AN XY: 74428

Gnomad4 AFR AF: 0.144

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.230

Alfa AF: 0.266 Hom.: 6398

Bravo AF: 0.218

Asia WGS AF: 0.243 AC: 844 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.45

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: rs2212361; hg19: chr11-94312323;