chr8-127308101-A-G

Position:

• chr8-127308101-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.149-13972A>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 0.149 in 152,224 control chromosomes in the GnomAD database, including 1,827 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 0.15 (1827 hom., cov: 33)
• Consequence: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-13972A>G		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-18041T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-18041T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22705 AN: 152106 Hom.: 1825 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.147

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.149 AC: 22723 AN: 152224 Hom.: 1827 Cov.: 33 AF XY: 0.157 AC XY: 11679 AN XY: 74418

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.147

Gnomad4 OTH AF: 0.131

Alfa AF: 0.146 Hom.: 2329

Bravo AF: 0.139

Asia WGS AF: 0.211 AC: 733 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16902094; hg19: chr8-128320346;