rs3217980

Positions:

• chr9-22006608-G-A

Variant summary

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

The NM_004936.4(CDKN2B):​c.157-361C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 152,146 control chromosomes in the GnomAD database, including 374 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 0.042 (374 hom., cov: 33)
• Consequence: CDKN2B NM_004936.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174

Genes affected

CDKN2B (HGNC:1788): (cyclin dependent kinase inhibitor 2B) This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated and deleted in a wide variety of tumors. This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

CDKN2B-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN2B	NM_004936.4	c.157-361C>T		intron_variant		ENST00000276925.7	NP_004927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN2B	ENST00000276925.7	c.157-361C>T		intron_variant		1	NM_004936.4	ENSP00000276925.6

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6405 AN: 152028 Hom.: 373 Cov.: 33

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0213

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.00217

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00666

Gnomad OTH AF: 0.0364

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

GnomAD4 genome AF: 0.0422 AC: 6418 AN: 152146 Hom.: 374 Cov.: 33 AF XY: 0.0411 AC XY: 3057 AN XY: 74380

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.0213

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.00217

Gnomad4 NFE AF: 0.00666

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0235 Hom.: 52

Bravo AF: 0.0470

Asia WGS AF: 0.0110 AC: 39 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.1
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3217980; hg19: chr9-22006607;