rs1801270

Positions:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000389.5(CDKN1A):c.93C>A(p.Ser31Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 1,611,622 control chromosomes in the GnomAD database, including 14,561 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.15 ( 2560 hom., cov: 32)

Exomes 𝑓: 0.094 ( 12001 hom. )

Consequence

CDKN1A
NM_000389.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.899

Variant links:

Genes affected

CDKN1A (HGNC:1784): (cyclin dependent kinase inhibitor 1A) This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-cyclin-dependent kinase2 or -cyclin-dependent kinase4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen, a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of cyclin-dependent kinase2, and may be instrumental in the execution of apoptosis following caspase activation. Mice that lack this gene have the ability to regenerate damaged or missing tissue. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Sep 2015]

CDKN1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.681613E-4).

BP6

Variant 6-36684194-C-A is Benign according to our data. Variant chr6-36684194-C-A is described in ClinVar as [Benign]. Clinvar id is 17565.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-36684194-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKN1A	NM_000389.5 linkuse as main transcript	c.93C>A	p.Ser31Arg	missense_variant	2/3	ENST00000244741.10	NP_000380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKN1A	ENST00000244741.10 linkuse as main transcript	c.93C>A	p.Ser31Arg	missense_variant	2/3	1	NM_000389.5	ENSP00000244741	P1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22686

AN:

152110

Hom.:

2560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.224

Gnomad ASJ

AF:

0.0841

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0601

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.141

GnomAD3 exomes

AF:

0.154

AC:

38469

AN:

249318

Hom.:

5612

AF XY:

0.140

AC XY:

18941

AN XY:

134984

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.348

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.491

Gnomad SAS exome

AF:

0.102

Gnomad FIN exome

AF:

0.0568

Gnomad NFE exome

AF:

0.0655

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.0937

AC:

136706

AN:

1459394

Hom.:

12001

Cov.:

AF XY:

0.0924

AC XY:

67077

AN XY:

726132

show subpopulations

Gnomad4 AFR exome

AF:

0.256

Gnomad4 AMR exome

AF:

0.332

Gnomad4 ASJ exome

AF:

0.0904

Gnomad4 EAS exome

AF:

0.480

Gnomad4 SAS exome

AF:

0.104

Gnomad4 FIN exome

AF:

0.0557

Gnomad4 NFE exome

AF:

0.0653

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.149

AC:

22716

AN:

152228

Hom.:

2560

Cov.:

AF XY:

0.153

AC XY:

11402

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.0841

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.122

Gnomad4 FIN

AF:

0.0601

Gnomad4 NFE

AF:

0.0657

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.0887

Hom.:

2061

Bravo

AF:

0.175

TwinsUK

AF:

0.0720

AC:

267

ALSPAC

AF:

0.0669

AC:

258

ESP6500AA

AF:

0.240

AC:

1057

ESP6500EA

AF:

0.0700

AC:

602

ExAC

AF:

0.146

AC:

17769

Asia WGS

AF:

0.258

AC:

897

AN:

3478

EpiCase

AF:

0.0693

EpiControl

AF:

0.0661

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CIP1/WAF1 TUMOR-ASSOCIATED POLYMORPHISM 1

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 01, 1996

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

2.4

DANN

Benign

0.85

DEOGEN2

Benign

0.049

T;T;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.28

.;T;.;.;.

MetaRNN

Benign

0.00027

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.0

N;N;N;N;N

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.33

PROVEAN

Benign

0.79

.;.;N;N;N

REVEL

Benign

0.24

Sift

Benign

1.0

.;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.22

MutPred

0.12

Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);Gain of solvent accessibility (P = 0.0766);

MPC

0.19

ClinPred

0.0071

GERP RS

-3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.49

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