chr6-22201365-C-T

Position:

• chr6-22201365-C-T

Variant summary

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

The XR_007059494.1(LOC124901275):​n.338C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,124 control chromosomes in the GnomAD database, including 582 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 0.081 (582 hom., cov: 32)
• Consequence: LOC124901275 XR_007059494.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

Genes affected

LOC124901275 (HGNC:):

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [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 (AMR) allele frequency at 95% confidence interval = 0.0873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901275	XR_007059494.1	n.338C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000688254.1	n.1152-12942C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12241 AN: 152006 Hom.: 581 Cov.: 32

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.0786

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

GnomAD4 genome AF: 0.0805 AC: 12249 AN: 152124 Hom.: 582 Cov.: 32 AF XY: 0.0844 AC XY: 6278 AN XY: 74348

Gnomad4 AFR AF: 0.0476

Gnomad4 AMR AF: 0.0913

Gnomad4 ASJ AF: 0.0320

Gnomad4 EAS AF: 0.0770

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.0856

Gnomad4 OTH AF: 0.0783

Alfa AF: 0.0788 Hom.: 448

Bravo AF: 0.0715

Asia WGS AF: 0.0720 AC: 252 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	5.8
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7751843; hg19: chr6-22201594;