9-22065658-G-C

Position:

• chr9-22065658-G-C

Variant summary

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

The ENST00000428597.6(CDKN2B-AS1):​n.2234-4G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.651 in 151,996 control chromosomes in the GnomAD database, including 32,458 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 0.65 (32457 hom., cov: 30)
  • Exomes 𝑓: 0.67 (1 hom.)
• Consequence: CDKN2B-AS1 ENST00000428597.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.168

Genes affected

CDKN2B-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B-AS1	NR_003529.4	n.2234-4G>C		splice_region_variant, intron_variant
CDKN2B-AS1	NR_047532.2	n.1075+9271G>C		intron_variant
CDKN2B-AS1	NR_047533.2	n.645-12021G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B-AS1	ENST00000428597.6	n.2234-4G>C		splice_region_variant, intron_variant		1
CDKN2B-AS1	ENST00000455933.7	n.749+9271G>C		intron_variant		1
CDKN2B-AS1	ENST00000577551.5	n.533+16430G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98824 AN: 151872 Hom.: 32437 Cov.: 30

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.676

GnomAD4 exome AF: 0.667 AC: 4 AN: 6 Hom.: 1 Cov.: 0 AF XY: 0.667 AC XY: 4 AN XY: 6

Gnomad4 AFR exome AF: 1.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.651 AC: 98884 AN: 151990 Hom.: 32457 Cov.: 30 AF XY: 0.653 AC XY: 48508 AN XY: 74278

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.760

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.604

Gnomad4 OTH AF: 0.671

Alfa AF: 0.612 Hom.: 3385

Bravo AF: 0.659

Asia WGS AF: 0.721 AC: 2506 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.1
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1333039; hg19: chr9-22065657;