chr6-21817734-G-C

Position:

• chr6-21817734-G-C

Variant summary

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

The NR_015410.2(CASC15):​n.647+14994G>C 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 0.752 in 152,160 control chromosomes in the GnomAD database, including 43,534 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 0.75 (43534 hom., cov: 33)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.943

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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.647+14994G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC15	ENST00000688254.1	n.550+34026G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.752 AC: 114364 AN: 152042 Hom.: 43479 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.802

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.769

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

GnomAD4 genome AF: 0.752 AC: 114467 AN: 152160 Hom.: 43534 Cov.: 33 AF XY: 0.750 AC XY: 55796 AN XY: 74378

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.592

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.761

Alfa AF: 0.713 Hom.: 4847

Bravo AF: 0.776

Asia WGS AF: 0.688 AC: 2394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6918975; hg19: chr6-21817965;