chr8-127343372-A-G

Position:

• chr8-127343372-A-G

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-560+3937A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,744 control chromosomes in the GnomAD database, including 14,807 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 (14807 hom., cov: 30)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.457+3937A>G		intron_variant
CASC8	NR_117100.1	n.1177-53312T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.547-20218T>C		intron_variant		1
CASC8	ENST00000502082.5	n.1177-53312T>C		intron_variant		1
PCAT1	ENST00000521586.2	n.289+3937A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66397 AN: 151624 Hom.: 14769 Cov.: 30

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.414

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.438 AC: 66487 AN: 151744 Hom.: 14807 Cov.: 30 AF XY: 0.438 AC XY: 32474 AN XY: 74144

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.414

Gnomad4 OTH AF: 0.480

Alfa AF: 0.417 Hom.: 16576

Bravo AF: 0.452

Asia WGS AF: 0.525 AC: 1823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13281615; hg19: chr8-128355618;