11-94590674-T-G

Position:

• chr11-94590674-T-G

Variant summary

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

The NM_152431.3(PIWIL4):​c.1026+1442T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,014 control chromosomes in the GnomAD database, including 6,409 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 0.29 (6409 hom., cov: 32)
• Consequence: PIWIL4 NM_152431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.107

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.411 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIWIL4	NM_152431.3	c.1026+1442T>G		intron_variant		ENST00000299001.11	NP_689644.2
PIWIL4-AS1	NR_135093.1	n.524-44828A>C		intron_variant, non_coding_transcript_variant
PIWIL4-AS1	NR_135094.1	n.437-44349A>C		intron_variant, non_coding_transcript_variant
PIWIL4-AS1	NR_135096.1	n.622+2793A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIWIL4	ENST00000299001.11	c.1026+1442T>G		intron_variant		1	NM_152431.3	ENSP00000299001	P1
PIWIL4-AS1	ENST00000536540.5	n.438-44828A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43597 AN: 151896 Hom.: 6397 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0945

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.287 AC: 43647 AN: 152014 Hom.: 6409 Cov.: 32 AF XY: 0.288 AC XY: 21425 AN XY: 74280

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.277

Alfa AF: 0.287 Hom.: 12207

Bravo AF: 0.282

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.4
DANN	Benign	0.36

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: rs7126782; hg19: chr11-94323840;