6-21968668-A-G

Variant names:

• chr6-21968668-A-G
• rs1928176
• ENST00000444265.6:n.200-10277A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444265.6(CASC15):​n.200-10277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,024 control chromosomes in the GnomAD database, including 17,868 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 0.46 (17868 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444265.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	NR_015410.2		n.782-10277A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.200-10277A>G		intron	N/A
	CASC15	ENST00000606851.5	TSL:2	n.751-10277A>G		intron	N/A
	CASC15	ENST00000607048.5	TSL:2	n.377-10277A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70314 AN: 151904 Hom.: 17863 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.463 AC: 70347 AN: 152024 Hom.: 17868 Cov.: 32 AF XY: 0.471 AC XY: 34970 AN XY: 74294

African (AFR) AF: 0.306 AC: 12684 AN: 41466

American (AMR) AF: 0.583 AC: 8919 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1409 AN: 3470

East Asian (EAS) AF: 0.964 AC: 4990 AN: 5174

South Asian (SAS) AF: 0.629 AC: 3030 AN: 4820

European-Finnish (FIN) AF: 0.491 AC: 5173 AN: 10532

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32598 AN: 67960

Other (OTH) AF: 0.469 AC: 990 AN: 2112

Alfa AF: 0.471 Hom.: 28283

Bravo AF: 0.464

Asia WGS AF: 0.752 AC: 2614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.19

Splicing

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

Other links and lift over

dbSNP: rs1928176; hg19: chr6-21968899;