rs2212361

Variant names:

• chr11-94579157-T-C
• rs2212361
• NM_152431.3:c.513+1665T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152431.3. 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
	PIWIL4	NM_152431.3	MANE Select	c.513+1665T>C		intron	N/A	NP_689644.2	Q7Z3Z4-1
	PIWIL4-AS1	NR_135093.1		n.524-33311A>G		intron	N/A
	PIWIL4-AS1	NR_135094.1		n.437-32832A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PIWIL4	ENST00000299001.11	TSL:1 MANE Select	c.513+1665T>C		intron	N/A	ENSP00000299001.6	Q7Z3Z4-1
	PIWIL4	ENST00000545603.1	TSL:4	c.306+1665T>C		intron	N/A	ENSP00000440499.1	F5GX26
	PIWIL4	ENST00000446230.6	TSL:2	n.432+1665T>C		intron	N/A	ENSP00000413838.2	Q7Z3Z4-2

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

African (AFR) AF: 0.144 AC: 5976 AN: 41566

American (AMR) AF: 0.205 AC: 3130 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1475 AN: 5182

South Asian (SAS) AF: 0.179 AC: 864 AN: 4826

European-Finnish (FIN) AF: 0.306 AC: 3235 AN: 10582

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.276 AC: 18791 AN: 67984

Other (OTH) AF: 0.230 AC: 486 AN: 2112

Alfa AF: 0.254 Hom.: 9003

Bravo AF: 0.218

Asia WGS AF: 0.243 AC: 844 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.7
DANN	Benign	0.45
PhyloP100		0.17
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: rs2212361; hg19: chr11-94312323;