8-127281221-A-G

Position:

• chr8-127281221-A-G

Variant summary

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

The NR_117099.1(CASC21):​n.148+36437A>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 0.813 in 152,226 control chromosomes in the GnomAD database, including 50,797 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 0.81 (50797 hom., cov: 33)
• Consequence: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.441

Genes affected

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC21	NR_117099.1	n.148+36437A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCAT1	ENST00000645463.1	n.856-11591A>G		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000644021.1	n.148+36437A>G		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000646670.1	n.1065-58060A>G		intron_variant, non_coding_transcript_variant
PCAT1	ENST00000647190.2	n.1192-11591A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123590 AN: 152108 Hom.: 50754 Cov.: 33

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.792

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.740

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.813 AC: 123688 AN: 152226 Hom.: 50797 Cov.: 33 AF XY: 0.803 AC XY: 59727 AN XY: 74412

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.792

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.740

Gnomad4 NFE AF: 0.795

Gnomad4 OTH AF: 0.810

Alfa AF: 0.798 Hom.: 20268

Bravo AF: 0.827

Asia WGS AF: 0.646 AC: 2247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs185852; hg19: chr8-128293466;