ENST00000444265.6:n.887+22823A>G

Variant names:

• chr6-22086063-A-G
• rs6901423
• ENST00000444265.6:n.887+22823A>G

Variant summary

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

The ENST00000444265.6(CASC15):​n.887+22823A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 151,888 control chromosomes in the GnomAD database, including 18,378 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 (18377 hom., cov: 32)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519
• Publications: 8 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]

RN7SKP240 (HGNC:45964): (RN7SK pseudogene 240)

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 (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1249-24684A>G		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.887+22823A>G		intron_variant	Intron 6 of 10	1
CASC15	ENST00000606851.5	n.1218-24684A>G		intron_variant	Intron 8 of 11	2
CASC15	ENST00000607048.5	n.844-24684A>G		intron_variant	Intron 7 of 11	2

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72646 AN: 151764 Hom.: 18369 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.500 AC: 3 AN: 6 Hom.: 1 AF XY: 0.500 AC XY: 3 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 3 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.478 AC: 72667 AN: 151882 Hom.: 18377 Cov.: 32 AF XY: 0.475 AC XY: 35246 AN XY: 74218

African (AFR) AF: 0.387 AC: 16021 AN: 41428

American (AMR) AF: 0.387 AC: 5896 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1536 AN: 3466

East Asian (EAS) AF: 0.138 AC: 709 AN: 5144

South Asian (SAS) AF: 0.422 AC: 2032 AN: 4816

European-Finnish (FIN) AF: 0.620 AC: 6540 AN: 10546

Middle Eastern (MID) AF: 0.565 AC: 165 AN: 292

European-Non Finnish (NFE) AF: 0.562 AC: 38165 AN: 67926

Other (OTH) AF: 0.459 AC: 966 AN: 2104

Alfa AF: 0.505 Hom.: 8959

Bravo AF: 0.456

Asia WGS AF: 0.277 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.76
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs6901423; hg19: chr6-22086292;