Variant 6-36677919-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001291549.3(CDKN1A):c.83A>G(p.Asp28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,345,436 control chromosomes in the GnomAD database, including 118,561 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 19399 hom., cov: 31)

Exomes 𝑓: 0.40 ( 99162 hom. )

Consequence

CDKN1A
NM_001291549.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

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:

CDKN1A (HGNC:):

CDKN1A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
CDKN1A	NM_001291549.3 linkuse as main transcript	c.83A>G	p.Asp28Gly	missense_variant	2/4	NP_001278478.1	P38936
CDKN1A	NM_001374509.1 linkuse as main transcript	c.83A>G	p.Asp28Gly	missense_variant	2/4	NP_001361438.1
CDKN1A	NM_078467.3 linkuse as main transcript	c.-20A>G		5_prime_UTR_variant	2/4	NP_510867.1	P38936A0A024RCX5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	Protein	UniProt
CDKN1A	ENST00000448526.6 linkuse as main transcript	c.-20A>G	5_prime_UTR_variant	2/4	3	ENSP00000409259.3	P38936
CDKN1A	ENST00000615513.4 linkuse as main transcript	c.-6+1395A>G	intron_variant		2	ENSP00000482768.1	P38936
CDKN1A	ENST00000459970.1 linkuse as main transcript	n.175A>G	non_coding_transcript_exon_variant	2/3	5
DINOL	ENST00000643333.1 linkuse as main transcript	n.641T>C	non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.486

AC:

73846

AN:

151896

Hom.:

19350

Cov.:

show subpopulations

Gnomad AFR

AF:

0.685

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.556

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.361

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.502

GnomAD3 exomes

AF:

0.427

AC:

54819

AN:

128402

Hom.:

12377

AF XY:

0.431

AC XY:

30330

AN XY:

70318

show subpopulations

Gnomad AFR exome

AF:

0.696

Gnomad AMR exome

AF:

0.335

Gnomad ASJ exome

AF:

0.553

Gnomad EAS exome

AF:

0.495

Gnomad SAS exome

AF:

0.447

Gnomad FIN exome

AF:

0.355

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.401

AC:

478550

AN:

1193422

Hom.:

99162

Cov.:

AF XY:

0.403

AC XY:

235478

AN XY:

584570

show subpopulations

Gnomad4 AFR exome

AF:

0.696

Gnomad4 AMR exome

AF:

0.341

Gnomad4 ASJ exome

AF:

0.547

Gnomad4 EAS exome

AF:

0.550

Gnomad4 SAS exome

AF:

0.449

Gnomad4 FIN exome

AF:

0.356

Gnomad4 NFE exome

AF:

0.382

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.486

AC:

73944

AN:

152014

Hom.:

19399

Cov.:

AF XY:

0.486

AC XY:

36088

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.686

Gnomad4 AMR

AF:

0.427

Gnomad4 ASJ

AF:

0.556

Gnomad4 EAS

AF:

0.521

Gnomad4 SAS

AF:

0.456

Gnomad4 FIN

AF:

0.361

Gnomad4 NFE

AF:

0.396

Gnomad4 OTH

AF:

0.508

Alfa

AF:

0.431

Hom.:

18065

Bravo

AF:

0.498

Asia WGS

AF:

0.508

AC:

1768

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.2

DANN

Benign

0.29

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over