rs16902126

Variant names:

• chr8-127370111-A-G
• rs16902126
• ENST00000501396.5:n.547-46957T>C

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-560+30676A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,006 control chromosomes in the GnomAD database, including 15,274 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 0.44 (15274 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

CASC21 (HGNC:49836): (cancer susceptibility 21)

ACMG classification

Verdict is Benign. Variant got -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 = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.458-22393A>G		intron_variant	Intron 3 of 3
CASC8	NR_117100.1	n.1176+50718T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.547-46957T>C		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+50718T>C		intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2	n.290-22393A>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66903 AN: 151888 Hom.: 15264 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.272

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.405

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

GnomAD4 genome AF: 0.440 AC: 66940 AN: 152006 Hom.: 15274 Cov.: 32 AF XY: 0.434 AC XY: 32252 AN XY: 74272

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.405

Alfa AF: 0.417 Hom.: 27535

Bravo AF: 0.436

Asia WGS AF: 0.307 AC: 1069 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.7
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16902126; hg19: chr8-128382357;