chr8-127310936-T-C

Position:

• chr8-127310936-T-C

Variant summary

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

The NR_117099.1(CASC21):​n.149-11137T>C 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 0.456 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: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.969

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

CASC21 (HGNC:):

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-11137T>C		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-20876A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-20876A>G		intron_variant, non_coding_transcript_variant		1

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

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.443

Alfa AF: 0.378 Hom.: 20691

Bravo AF: 0.468

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs445114; hg19: chr8-128323181;