rs283720

chr8-127297720-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.149-24353A>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 0.617 in 152,130 control chromosomes in the GnomAD database, including 30,393 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 0.62 (30393 hom., cov: 33)
• Consequence: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC21	NR_117099.1	n.149-24353A>G		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-7660T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-7660T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93861 AN: 152012 Hom.: 30384 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.617 AC: 93902 AN: 152130 Hom.: 30393 Cov.: 33 AF XY: 0.611 AC XY: 45427 AN XY: 74370

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.665

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.590

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.726

Gnomad4 OTH AF: 0.632

Alfa AF: 0.704 Hom.: 55008

Bravo AF: 0.612

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.77
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs283720; hg19: chr8-128309965;