Variant 9-22006349-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004936.4(CDKN2B):c.157-102G>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 1,496,034 control chromosomes in the GnomAD database, including 9,842 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 1880 hom., cov: 33)

Exomes 𝑓: 0.10 ( 7962 hom. )

Consequence

CDKN2B
NM_004936.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -4.31

Variant links:

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 links:

CDKN2B-AS1 (HGNC:34341): (CDKN2B antisense RNA 1) This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer's disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960). [provided by RefSeq, May 2014]

CDKN2B-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-22006349-C-T is Benign according to our data. Variant chr9-22006349-C-T is described in ClinVar as [Benign]. Clinvar id is 812646.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDKN2B	NM_004936.4 linkuse as main transcript	c.157-102G>A		intron_variant		ENST00000276925.7
CDKN2B-AS1	NR_003529.3 linkuse as main transcript	n.371+11188C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDKN2B	ENST00000276925.7 linkuse as main transcript	c.157-102G>A		intron_variant		1	NM_004936.4	P1	P42772-1
CDKN2B-AS1	ENST00000650946.1 linkuse as main transcript	n.29+11188C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.143

AC:

21684

AN:

152114

Hom.:

1869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0988

Gnomad ASJ

AF:

0.110

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0835

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0998

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.103

AC:

138758

AN:

1343802

Hom.:

7962

AF XY:

0.104

AC XY:

69235

AN XY:

668514

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 AMR exome

AF:

0.0676

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0785

Gnomad4 NFE exome

AF:

0.0953

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.143

AC:

21732

AN:

152232

Hom.:

1880

Cov.:

AF XY:

0.142

AC XY:

10558

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.0987

Gnomad4 ASJ

AF:

0.110

Gnomad4 EAS

AF:

0.217

Gnomad4 SAS

AF:

0.113

Gnomad4 FIN

AF:

0.0835

Gnomad4 NFE

AF:

0.0998

Gnomad4 OTH

AF:

0.136

Alfa

AF:

0.112

Hom.:

328

Bravo

AF:

0.147

Asia WGS

AF:

0.148

AC:

514

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Three Vessel Coronary Disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.049

DANN

Benign

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over