chr11-94621313-C-T

Position:

• chr11-94621313-C-T

Variant summary

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

The NM_152431.3(PIWIL4):​c.*321C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 227,546 control chromosomes in the GnomAD database, including 27,801 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 0.49 (17936 hom., cov: 32)
  • Exomes 𝑓: 0.51 (9865 hom.)
• Consequence: PIWIL4 NM_152431.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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 (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIWIL4	NM_152431.3	c.*321C>T		3_prime_UTR_variant	20/20	ENST00000299001.11
PIWIL4-AS1	NR_135093.1	n.523+54323G>A		intron_variant, non_coding_transcript_variant
PIWIL4-AS1	NR_135094.1	n.436+54323G>A		intron_variant, non_coding_transcript_variant
PIWIL4-AS1	NR_135096.1	n.524-27748G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIWIL4	ENST00000299001.11	c.*321C>T		3_prime_UTR_variant	20/20	1	NM_152431.3	P1
PIWIL4-AS1	ENST00000536540.5	n.437+54323G>A		intron_variant, non_coding_transcript_variant		3
PIWIL4	ENST00000446230.6	c.*1636C>T		3_prime_UTR_variant, NMD_transcript_variant	19/19	2
PIWIL4-AS1	ENST00000537874.1	n.436+54323G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73807 AN: 151836 Hom.: 17920 Cov.: 32

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.492

GnomAD4 exome AF: 0.511 AC: 38661 AN: 75592 Hom.: 9865 Cov.: 0 AF XY: 0.509 AC XY: 19830 AN XY: 38994

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.558

Gnomad4 EAS exome AF: 0.489

Gnomad4 SAS exome AF: 0.466

Gnomad4 FIN exome AF: 0.539

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.524

GnomAD4 genome AF: 0.486 AC: 73866 AN: 151954 Hom.: 17936 Cov.: 32 AF XY: 0.485 AC XY: 36058 AN XY: 74272

Gnomad4 AFR AF: 0.455

Gnomad4 AMR AF: 0.486

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.493

Alfa AF: 0.496 Hom.: 19141

Bravo AF: 0.486

Asia WGS AF: 0.465 AC: 1619 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.51

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: rs508485; hg19: chr11-94354479;