8-127417476-T-C

Position:

• chr8-127417476-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_117100.1(CASC8):​n.1176+3353A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 155,558 control chromosomes in the GnomAD database, including 31,557 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 0.63 (30791 hom., cov: 31)
  • Exomes 𝑓: 0.62 (766 hom.)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0360

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+3353A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5	n.1176+3353A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.633 AC: 95895 AN: 151572 Hom.: 30779 Cov.: 31

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.653

GnomAD4 exome AF: 0.619 AC: 2394 AN: 3868 Hom.: 766 Cov.: 0 AF XY: 0.640 AC XY: 1138 AN XY: 1778

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.648

Gnomad4 ASJ exome AF: 0.579

Gnomad4 EAS exome AF: 0.738

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.626

GnomAD4 genome AF: 0.632 AC: 95942 AN: 151690 Hom.: 30791 Cov.: 31 AF XY: 0.640 AC XY: 47410 AN XY: 74124

Gnomad4 AFR AF: 0.532

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.615

Gnomad4 EAS AF: 0.795

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.655

Alfa AF: 0.651 Hom.: 54363

Bravo AF: 0.629

Asia WGS AF: 0.716 AC: 2487 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs6985419; hg19: chr8-128429721;