dbSNP rs762624: CDKN1A:c.-26A>C (chr6-36677811-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001291549.3(CDKN1A):c.-26A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,222,592 control chromosomes in the GnomAD database, including 60,047 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 0.35 ( 10279 hom., cov: 31)

Exomes 𝑓: 0.29 ( 49768 hom. )

Consequence

CDKN1A
NM_001291549.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.627

Publications

34 publications found

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:

DINOL (HGNC:53146): (damage induced long noncoding RNA)

DINOL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291549.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
CDKN1A	NM_001291549.3	c.-26A>C	5_prime_UTR	Exon 2 of 4	NP_001278478.1
CDKN1A	NM_001374509.1	c.-26A>C	5_prime_UTR	Exon 2 of 4	NP_001361438.1
CDKN1A	NM_001374510.1	c.34+1241A>C	intron	N/A	NP_001361439.1

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
CDKN1A	ENST00000911805.1	c.-128A>C	5_prime_UTR	Exon 2 of 4	ENSP00000581864.1
CDKN1A	ENST00000911808.1	c.-128A>C	5_prime_UTR	Exon 1 of 3	ENSP00000581867.1
CDKN1A	ENST00000911809.1	c.-128A>C	5_prime_UTR	Exon 2 of 4	ENSP00000581868.1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53524

AN:

151810

Hom.:

10263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.461

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.434

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.371

GnomAD2 exomes

AF:

0.375

AC:

47723

AN:

127384

AF XY:

0.370

show subpopulations

Gnomad AFR exome

AF:

0.475

Gnomad AMR exome

AF:

0.499

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.593

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.270

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.292

AC:

313157

AN:

1070664

Hom.:

49768

Cov.:

AF XY:

0.296

AC XY:

156704

AN XY:

530170

show subpopulations

African (AFR)

AF:

0.472

AC:

11805

AN:

24990

American (AMR)

AF:

0.493

AC:

14962

AN:

30370

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

6576

AN:

19860

East Asian (EAS)

AF:

0.605

AC:

14102

AN:

23316

South Asian (SAS)

AF:

0.391

AC:

28860

AN:

73864

European-Finnish (FIN)

AF:

0.228

AC:

3087

AN:

13544

Middle Eastern (MID)

AF:

0.358

AC:

1642

AN:

4588

European-Non Finnish (NFE)

AF:

0.261

AC:

218357

AN:

837064

Other (OTH)

AF:

0.320

AC:

13766

AN:

43068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

9999

19997

29996

39994

49993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8074

16148

24222

32296

40370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.353

AC:

53575

AN:

151928

Hom.:

10279

Cov.:

AF XY:

0.354

AC XY:

26314

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.460

AC:

19045

AN:

41386

American (AMR)

AF:

0.435

AC:

6631

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1143

AN:

3468

East Asian (EAS)

AF:

0.598

AC:

3083

AN:

5156

South Asian (SAS)

AF:

0.411

AC:

1972

AN:

4800

European-Finnish (FIN)

AF:

0.237

AC:

2499

AN:

10562

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18079

AN:

67978

Other (OTH)

AF:

0.378

AC:

800

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1687

3373

5060

6746

8433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.301

Hom.:

14462

Bravo

AF:

0.375

Asia WGS

AF:

0.506

AC:

1758

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.63

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over