rs4871789

Variant names:

• chr8-127415816-A-G
• rs4871789
• ENST00000501396.6:n.546+5013T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-127415816-A-G
• chr8-127415816-A-T

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+5013T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 1,465,806 control chromosomes in the GnomAD database, including 187,860 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 0.45 (16732 hom., cov: 33)
  • Exomes 𝑓: 0.51 (171128 hom.)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• Publications: 19 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1B	NM_001395745.1	c.-51A>G		5_prime_UTR_variant	Exon 2 of 2		NP_001382674.1
CASC8	NR_117100.1	n.1176+5013T>C		intron_variant	Intron 5 of 5
POU5F1B	NM_001159542.3	c.-51A>G		upstream_gene_variant		ENST00000696633.1	NP_001153014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1B	ENST00000696633.1	c.-51A>G		upstream_gene_variant			NM_001159542.3	ENSP00000512769.1

Frequencies

GnomAD3 genomes AF: 0.450 AC: 68339 AN: 151990 Hom.: 16727 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.507 AC: 665702 AN: 1313698 Hom.: 171128 Cov.: 48 AF XY: 0.509 AC XY: 325335 AN XY: 639210

African (AFR) AF: 0.235 AC: 6717 AN: 28566

American (AMR) AF: 0.609 AC: 13209 AN: 21678

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 8615 AN: 19632

East Asian (EAS) AF: 0.656 AC: 23056 AN: 35144

South Asian (SAS) AF: 0.584 AC: 38027 AN: 65126

European-Finnish (FIN) AF: 0.486 AC: 21943 AN: 45142

Middle Eastern (MID) AF: 0.489 AC: 1965 AN: 4018

European-Non Finnish (NFE) AF: 0.504 AC: 524725 AN: 1040200

Other (OTH) AF: 0.506 AC: 27445 AN: 54192

GnomAD4 genome AF: 0.449 AC: 68360 AN: 152108 Hom.: 16732 Cov.: 33 AF XY: 0.456 AC XY: 33934 AN XY: 74346

African (AFR) AF: 0.253 AC: 10481 AN: 41500

American (AMR) AF: 0.576 AC: 8811 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1520 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3334 AN: 5162

South Asian (SAS) AF: 0.570 AC: 2750 AN: 4822

European-Finnish (FIN) AF: 0.496 AC: 5250 AN: 10582

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34652 AN: 67962

Other (OTH) AF: 0.481 AC: 1015 AN: 2108

Alfa AF: 0.492 Hom.: 73315

Bravo AF: 0.446

Asia WGS AF: 0.585 AC: 2033 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.79
PhyloP100		0.48
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4871789; hg19: chr8-128428061; COSMIC: COSV66966705; COSMIC: COSV66966705;