8-127310936-T-C

Variant names:

• chr8-127310936-T-C
• rs445114
• ENST00000501396.6:n.686+12079A>G

Variant summary

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

The ENST00000501396.6(CASC8):​n.686+12079A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,166 control chromosomes in the GnomAD database, including 17,158 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 0.46 (17158 hom., cov: 34)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969
• Publications: 97 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]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC21	NR_117099.1		n.149-11137T>C		intron	N/A
	CASC8	NR_117100.1		n.1177-20876A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.686+12079A>G		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1177-20876A>G		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.547-20876A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69241 AN: 152048 Hom.: 17126 Cov.: 34

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.456 AC: 69324 AN: 152166 Hom.: 17158 Cov.: 34 AF XY: 0.454 AC XY: 33785 AN XY: 74396

African (AFR) AF: 0.659 AC: 27334 AN: 41482

American (AMR) AF: 0.382 AC: 5842 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2323 AN: 5184

South Asian (SAS) AF: 0.518 AC: 2498 AN: 4824

European-Finnish (FIN) AF: 0.331 AC: 3502 AN: 10586

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24789 AN: 68008

Other (OTH) AF: 0.443 AC: 938 AN: 2116

Alfa AF: 0.393 Hom.: 50340

Bravo AF: 0.468

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.055
DANN	Benign	0.73
PhyloP100		-0.97

Splicing

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

Other links and lift over

dbSNP: rs445114; hg19: chr8-128323181;