chr6-22086845-T-A

Variant names:

• chr6-22086845-T-A
• rs12212674
• ENST00000444265.6:n.887+23605T>A

Variant summary

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

The ENST00000444265.6(CASC15):​n.887+23605T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 150,726 control chromosomes in the GnomAD database, including 18,289 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 0.48 (18289 hom., cov: 30)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 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.1249-23902T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.887+23605T>A		intron	N/A
	CASC15	ENST00000606851.5	TSL:2	n.1218-23902T>A		intron	N/A
	CASC15	ENST00000607048.5	TSL:2	n.844-23902T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72336 AN: 150630 Hom.: 18280 Cov.: 30

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.462

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

GnomAD4 genome AF: 0.480 AC: 72357 AN: 150726 Hom.: 18289 Cov.: 30 AF XY: 0.477 AC XY: 35093 AN XY: 73558

African (AFR) AF: 0.387 AC: 15838 AN: 40970

American (AMR) AF: 0.388 AC: 5857 AN: 15102

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1534 AN: 3466

East Asian (EAS) AF: 0.142 AC: 722 AN: 5078

South Asian (SAS) AF: 0.422 AC: 2017 AN: 4780

European-Finnish (FIN) AF: 0.632 AC: 6479 AN: 10254

Middle Eastern (MID) AF: 0.580 AC: 167 AN: 288

European-Non Finnish (NFE) AF: 0.563 AC: 38145 AN: 67786

Other (OTH) AF: 0.458 AC: 959 AN: 2094

Alfa AF: 0.515 Hom.: 2558

Bravo AF: 0.455

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.50
PhyloP100		0.19

Splicing

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

Other links and lift over

dbSNP: rs12212674; hg19: chr6-22087074;