rs1034071

Variant names:

• chr6-22097146-T-C
• rs1034071
• ENST00000444265.6:n.888-13601T>C

Variant summary

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

The ENST00000444265.6(CASC15):​n.888-13601T>C 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 151,994 control chromosomes in the GnomAD database, including 18,383 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 (18383 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1249-13601T>C		intron_variant	Intron 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.888-13601T>C		intron_variant	Intron 6 of 10	1
CASC15	ENST00000606851.5	n.1218-13601T>C		intron_variant	Intron 8 of 11	2
CASC15	ENST00000607048.5	n.844-13601T>C		intron_variant	Intron 7 of 11	2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72912 AN: 151876 Hom.: 18376 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.555

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: 72934 AN: 151994 Hom.: 18383 Cov.: 32 AF XY: 0.476 AC XY: 35389 AN XY: 74300

African (AFR) AF: 0.405 AC: 16805 AN: 41458

American (AMR) AF: 0.383 AC: 5849 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1517 AN: 3468

East Asian (EAS) AF: 0.139 AC: 718 AN: 5184

South Asian (SAS) AF: 0.421 AC: 2025 AN: 4806

European-Finnish (FIN) AF: 0.624 AC: 6581 AN: 10554

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.555 AC: 37669 AN: 67932

Other (OTH) AF: 0.457 AC: 968 AN: 2116

Alfa AF: 0.521 Hom.: 11324

Bravo AF: 0.459

Asia WGS AF: 0.276 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.65
DANN	Benign	0.46
PhyloP100		-0.26

Splicing

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

Other links and lift over

dbSNP: rs1034071; hg19: chr6-22097375;