chr6-22069847-G-A

Position:

• chr6-22069847-G-A

Variant summary

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

The NR_015410.2(CASC15):​n.1248+13157G>A 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 0.0829 in 152,002 control chromosomes in the GnomAD database, including 1,036 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 0.083 (1036 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

Genes affected

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=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1248+13157G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000688254.1	n.1151+13157G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0828 AC: 12580 AN: 151884 Hom.: 1031 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0829 AC: 12597 AN: 152002 Hom.: 1036 Cov.: 32 AF XY: 0.0835 AC XY: 6201 AN XY: 74306

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.0565

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0177

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0332 Hom.: 350

Bravo AF: 0.0909

Asia WGS AF: 0.115 AC: 397 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.7
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9295533; hg19: chr6-22070076;