rs13248944

Variant names:

• chr8-127408313-T-C
• rs13248944
• ENST00000501396.6:n.546+12516A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-127408313-T-C
• chr8-127408313-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645438.1(POU5F1B):​c.-559-6575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 151,966 control chromosomes in the GnomAD database, including 129 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 0.036 (129 hom., cov: 28)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.494
• Publications: 4 publications found

Genes affected

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

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0559 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
	CASC8	NR_117100.1		n.1176+12516A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+12516A>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+12516A>G		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+12516A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0361 AC: 5477 AN: 151848 Hom.: 129 Cov.: 28

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0628

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.0445

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0361 AC: 5479 AN: 151966 Hom.: 129 Cov.: 28 AF XY: 0.0380 AC XY: 2825 AN XY: 74266

African (AFR) AF: 0.0110 AC: 456 AN: 41420

American (AMR) AF: 0.0175 AC: 268 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3472

East Asian (EAS) AF: 0.0615 AC: 317 AN: 5158

South Asian (SAS) AF: 0.0452 AC: 217 AN: 4806

European-Finnish (FIN) AF: 0.0870 AC: 916 AN: 10526

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0441 AC: 3001 AN: 67990

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0359 Hom.: 124

Bravo AF: 0.0301

Asia WGS AF: 0.0420 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.65
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs13248944; hg19: chr8-128420558;