rs12523974

Positions:

• chr6-22073692-G-A
• chr6-22073692-G-C

Variant summary

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

The ENST00000444265.6(CASC15):​n.887+10452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,098 control chromosomes in the GnomAD database, including 2,326 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 0.11 (2326 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

Genes affected

CASC15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1248+17002G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.887+10452G>A		intron_variant		1
CASC15	ENST00000606851.5	n.1217+17002G>A		intron_variant		2
CASC15	ENST00000607048.5	n.843+17002G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16315 AN: 151980 Hom.: 2326 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0741

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.107 AC: 16343 AN: 152098 Hom.: 2326 Cov.: 32 AF XY: 0.117 AC XY: 8691 AN XY: 74354

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.0314

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0741

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.0922

Alfa AF: 0.0167 Hom.: 10

Bravo AF: 0.126

Asia WGS AF: 0.305 AC: 1058 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0090
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12523974; hg19: chr6-22073921;