chr8-127399212-T-G

Variant names:

• chr8-127399212-T-G
• rs10505475
• ENST00000501396.6:n.546+21617A>C

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+21617A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 152,212 control chromosomes in the GnomAD database, including 461 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 0.068 (461 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501396.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_117100.1		n.1176+21617A>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+21617A>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+21617A>C		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+21617A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0680 AC: 10336 AN: 152094 Hom.: 459 Cov.: 33

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.0468

Gnomad FIN AF: 0.0891

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0442

Gnomad OTH AF: 0.0556

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0679 AC: 10340 AN: 152212 Hom.: 461 Cov.: 33 AF XY: 0.0684 AC XY: 5092 AN XY: 74422

African (AFR) AF: 0.122 AC: 5065 AN: 41522

American (AMR) AF: 0.0273 AC: 418 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0493 AC: 171 AN: 3470

East Asian (EAS) AF: 0.0617 AC: 320 AN: 5184

South Asian (SAS) AF: 0.0473 AC: 228 AN: 4824

European-Finnish (FIN) AF: 0.0891 AC: 944 AN: 10592

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0442 AC: 3007 AN: 68010

Other (OTH) AF: 0.0550 AC: 116 AN: 2110

Alfa AF: 0.0483 Hom.: 144

Bravo AF: 0.0656

Asia WGS AF: 0.0510 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		0.025
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: rs10505475; hg19: chr8-128411457;