ENST00000501396.6:n.546+3812C>G

Variant names:

• chr8-127417017-G-C
• rs9297754
• ENST00000501396.6:n.546+3812C>G

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+3812C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.768 in 1,552,980 control chromosomes in the GnomAD database, including 459,899 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 0.73 (41718 hom., cov: 28)
  • Exomes 𝑓: 0.77 (418181 hom.)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.358
• Publications: 6 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 = 0.821 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
	POU5F1B	NM_001395745.1		c.*71G>C		3_prime_UTR	Exon 2 of 2	NP_001382674.1
	CASC8	NR_117100.1		n.1176+3812C>G		intron	N/A
	POU5F1B	NM_001159542.3	MANE Select	c.*71G>C		downstream_gene	N/A	NP_001153014.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+3812C>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+3812C>G		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+3812C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111382 AN: 151580 Hom.: 41708 Cov.: 28

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.853

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.771

GnomAD4 exome AF: 0.771 AC: 1080840 AN: 1401280 Hom.: 418181 Cov.: 40 AF XY: 0.772 AC XY: 533683 AN XY: 691438

African (AFR) AF: 0.572 AC: 18271 AN: 31916

American (AMR) AF: 0.787 AC: 28265 AN: 35934

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 20188 AN: 25144

East Asian (EAS) AF: 0.834 AC: 30318 AN: 36340

South Asian (SAS) AF: 0.758 AC: 60147 AN: 79342

European-Finnish (FIN) AF: 0.843 AC: 41800 AN: 49602

Middle Eastern (MID) AF: 0.842 AC: 4222 AN: 5016

European-Non Finnish (NFE) AF: 0.771 AC: 832550 AN: 1079926

Other (OTH) AF: 0.776 AC: 45079 AN: 58060

GnomAD4 genome AF: 0.735 AC: 111437 AN: 151700 Hom.: 41718 Cov.: 28 AF XY: 0.742 AC XY: 55018 AN XY: 74122

African (AFR) AF: 0.583 AC: 24115 AN: 41332

American (AMR) AF: 0.793 AC: 12097 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 2814 AN: 3472

East Asian (EAS) AF: 0.842 AC: 4329 AN: 5142

South Asian (SAS) AF: 0.738 AC: 3533 AN: 4788

European-Finnish (FIN) AF: 0.853 AC: 8968 AN: 10514

Middle Eastern (MID) AF: 0.842 AC: 246 AN: 292

European-Non Finnish (NFE) AF: 0.780 AC: 52985 AN: 67888

Other (OTH) AF: 0.771 AC: 1622 AN: 2104

Alfa AF: 0.749 Hom.: 5102

Bravo AF: 0.725

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.79
PhyloP100		-0.36
Mutation Taster		=100/0	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: rs9297754; hg19: chr8-128429262; COSMIC: COSV66966990; COSMIC: COSV66966990;