6-22096132-C-T

Variant names:

• chr6-22096132-C-T
• rs196048
• ENST00000444265.6:n.888-14615C>T

Variant summary

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

The ENST00000444265.6(CASC15):​n.888-14615C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,060 control chromosomes in the GnomAD database, including 41,271 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 0.73 (41271 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.902 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.1249-14615C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.888-14615C>T		intron	N/A
	CASC15	ENST00000606851.5	TSL:2	n.1218-14615C>T		intron	N/A
	CASC15	ENST00000607048.5	TSL:2	n.844-14615C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110262 AN: 151942 Hom.: 41220 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.671

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

GnomAD4 genome AF: 0.726 AC: 110364 AN: 152060 Hom.: 41271 Cov.: 32 AF XY: 0.729 AC XY: 54194 AN XY: 74316

African (AFR) AF: 0.910 AC: 37754 AN: 41504

American (AMR) AF: 0.693 AC: 10589 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1874 AN: 3472

East Asian (EAS) AF: 0.863 AC: 4465 AN: 5174

South Asian (SAS) AF: 0.733 AC: 3528 AN: 4812

European-Finnish (FIN) AF: 0.729 AC: 7702 AN: 10558

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42205 AN: 67956

Other (OTH) AF: 0.664 AC: 1401 AN: 2110

Alfa AF: 0.643 Hom.: 16150

Bravo AF: 0.732

Asia WGS AF: 0.711 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.39
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs196048; hg19: chr6-22096361;