chr8-127325027-T-TAC

Position:

• chr8-127325027-T-TAC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NR_117099.1(CASC21):​n.302+2802_302+2803dup 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 0.0239 in 36,346 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: 𝑓 0.024 (2 hom., cov: 25)
• Consequence: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.131

Genes affected

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

CASC21 (HGNC:):

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0239 (869/36346) while in subpopulation NFE AF= 0.0326 (599/18392). AF 95% confidence interval is 0.0304. There are 2 homozygotes in gnomad4. There are 429 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.302+2802_302+2803dup		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-34968_1177-34967insGT		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-34968_1177-34967insGT		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0240 AC: 870 AN: 36294 Hom.: 2 Cov.: 25

Gnomad AFR AF: 0.00627

Gnomad AMI AF: 0.00311

Gnomad AMR AF: 0.0145

Gnomad ASJ AF: 0.00117

Gnomad EAS AF: 0.000500

Gnomad SAS AF: 0.0130

Gnomad FIN AF: 0.0686

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0326

Gnomad OTH AF: 0.0126

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

GnomAD4 genome AF: 0.0239 AC: 869 AN: 36346 Hom.: 2 Cov.: 25 AF XY: 0.0248 AC XY: 429 AN XY: 17284

Gnomad4 AFR AF: 0.00623

Gnomad4 AMR AF: 0.0144

Gnomad4 ASJ AF: 0.00117

Gnomad4 EAS AF: 0.000502

Gnomad4 SAS AF: 0.0117

Gnomad4 FIN AF: 0.0686

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0124

Alfa AF: 0.00864 Hom.: 1

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial prostate cancer Other:1

association, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201361304; hg19: chr8-128337272;