ENST00000501396.6:n.547-1842C>A

Variant names:

• chr8-127324996-G-T
• rs377649
• ENST00000501396.6:n.547-1842C>A

Variant summary

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

The ENST00000501396.6(CASC8):​n.547-1842C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 150,880 control chromosomes in the GnomAD database, including 20,096 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 0.51 (20096 hom., cov: 30)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• 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]

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=-0.51).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 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
	CASC21	NR_117099.1		n.302+2770G>T		intron	N/A
	CASC8	NR_117100.1		n.1177-34936C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.547-1842C>A		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1177-34936C>A		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.547-34936C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77298 AN: 150764 Hom.: 20068 Cov.: 30

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.513 AC: 77382 AN: 150880 Hom.: 20096 Cov.: 30 AF XY: 0.523 AC XY: 38536 AN XY: 73666

African (AFR) AF: 0.475 AC: 19454 AN: 40986

American (AMR) AF: 0.504 AC: 7630 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.493 AC: 1706 AN: 3460

East Asian (EAS) AF: 0.697 AC: 3606 AN: 5170

South Asian (SAS) AF: 0.674 AC: 3219 AN: 4778

European-Finnish (FIN) AF: 0.582 AC: 5983 AN: 10282

Middle Eastern (MID) AF: 0.528 AC: 153 AN: 290

European-Non Finnish (NFE) AF: 0.500 AC: 33902 AN: 67776

Other (OTH) AF: 0.518 AC: 1082 AN: 2088

Alfa AF: 0.505 Hom.: 10550

Bravo AF: 0.499

Asia WGS AF: 0.695 AC: 2411 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.2
DANN	Benign	0.96
PhyloP100		-0.063

Splicing

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

Other links and lift over

dbSNP: rs377649; hg19: chr8-128337241;