8-127391269-T-G

Variant names:

• chr8-127391269-T-G
• rs7844673
• ENST00000501396.6:n.546+29560A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000645438.1(POU5F1B):​c.-559-23619T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,206 control chromosomes in the GnomAD database, including 563 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 0.079 (563 hom., cov: 32)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645438.1. 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
	CASC21	NR_117099.1		n.458-1235T>G		intron	N/A
	CASC8	NR_117100.1		n.1176+29560A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+29560A>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+29560A>C		intron	N/A
	PCAT1	ENST00000521586.2	TSL:1	n.290-1235T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12041 AN: 152088 Hom.: 560 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0792 AC: 12060 AN: 152206 Hom.: 563 Cov.: 32 AF XY: 0.0802 AC XY: 5970 AN XY: 74406

African (AFR) AF: 0.114 AC: 4725 AN: 41514

American (AMR) AF: 0.0452 AC: 692 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0831 AC: 288 AN: 3464

East Asian (EAS) AF: 0.0696 AC: 360 AN: 5170

South Asian (SAS) AF: 0.112 AC: 541 AN: 4816

European-Finnish (FIN) AF: 0.0892 AC: 947 AN: 10612

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0621 AC: 4222 AN: 68006

Other (OTH) AF: 0.0781 AC: 165 AN: 2114

Alfa AF: 0.0631 Hom.: 713

Bravo AF: 0.0753

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.82
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7844673; hg19: chr8-128403514;