chr8-127391642-G-A

Variant names:

• chr8-127391642-G-A
• rs10956365
• ENST00000501396.6:n.546+29187C>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+29187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,184 control chromosomes in the GnomAD database, including 2,059 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 0.15 (2059 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.458-862G>A		intron_variant	Intron 3 of 3
CASC8	NR_117100.1	n.1176+29187C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.546+29187C>T		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+29187C>T		intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2	n.290-862G>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22898 AN: 152066 Hom.: 2055 Cov.: 32

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.150 AC: 22903 AN: 152184 Hom.: 2059 Cov.: 32 AF XY: 0.152 AC XY: 11336 AN XY: 74402

African (AFR) AF: 0.0595 AC: 2470 AN: 41522

American (AMR) AF: 0.110 AC: 1683 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 727 AN: 3470

East Asian (EAS) AF: 0.146 AC: 760 AN: 5194

South Asian (SAS) AF: 0.146 AC: 706 AN: 4820

European-Finnish (FIN) AF: 0.265 AC: 2806 AN: 10572

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13140 AN: 68006

Other (OTH) AF: 0.152 AC: 321 AN: 2108

Alfa AF: 0.165 Hom.: 2972

Bravo AF: 0.135

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.3
DANN	Benign	0.66
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs10956365; hg19: chr8-128403887;