chr6-22191463-G-C

Position:

• chr6-22191463-G-C

Variant summary

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

The ENST00000444265.6(CASC15):​n.1062-104G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 152,262 control chromosomes in the GnomAD database, including 123 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 0.029 (123 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617

Genes affected

CASC15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC15	NR_015410.2	n.1488-104G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.1062-104G>C		intron_variant		1
CASC15	ENST00000561912.3	n.199+44393G>C		intron_variant		5
CASC15	ENST00000567753.2	n.89-22844G>C		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4339 AN: 152144 Hom.: 120 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.0846

Gnomad AMR AF: 0.0161

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0597

Gnomad FIN AF: 0.0137

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0176

Gnomad OTH AF: 0.0197

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 14 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 14

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0286 AC: 4348 AN: 152262 Hom.: 123 Cov.: 32 AF XY: 0.0297 AC XY: 2208 AN XY: 74434

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.0135

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.0595

Gnomad4 FIN AF: 0.0137

Gnomad4 NFE AF: 0.0176

Gnomad4 OTH AF: 0.0209

Alfa AF: 0.0191 Hom.: 7

Bravo AF: 0.0289

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.6
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10498707; hg19: chr6-22191692;