rs6939340

chr6-22139775-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_015410.2(CASC15):n.1422+28855A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,118 control chromosomes in the GnomAD database, including 30,806 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 0.62 (30806 hom., cov: 32)
• Consequence: CASC15 NR_015410.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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]

NBAT1 (HGNC:49075): (neuroblastoma associated transcript 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC15	NR_015410.2	n.1422+28855A>G		intron_variant, non_coding_transcript_variant
NBAT1	NR_034143.1	n.228-3106T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBAT1	ENST00000566912.2	n.228-3106T>C		intron_variant, non_coding_transcript_variant		2
CASC15	ENST00000688254.1	n.1152-74532A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93666 AN: 152000 Hom.: 30753 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.616 AC: 93773 AN: 152118 Hom.: 30806 Cov.: 32 AF XY: 0.621 AC XY: 46154 AN XY: 74360

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.630

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.631

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.572

Alfa AF: 0.500 Hom.: 44492

Bravo AF: 0.627

Asia WGS AF: 0.648 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.011
Dann	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6939340; hg19: chr6-22140004;