Genetic Variant PRKACB:c.*643A>C (chr1-84205133-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_001300916.2(PRKACB):c.*643A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 979,392 control chromosomes in the GnomAD database, including 141,207 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 0.43 ( 15926 hom., cov: 32)

Exomes 𝑓: 0.55 ( 125281 hom. )

Consequence

PRKACB
NM_001300916.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.608

Variant links:

Genes affected

PRKACB (HGNC:9381): (protein kinase cAMP-activated catalytic subunit beta) The protein encoded by this gene is a member of the serine/threonine protein kinase family. The encoded protein is a catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase, which mediates signalling though cAMP. cAMP signaling is important to a number of processes, including cell proliferaton and differentiation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2014]

PRKACB links:

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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=-0.81).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_182948.4 link	c.906+2328A>C		intron_variant	Intron 8 of 9	ENST00000370685.7	NP_891993.1	P22694-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370685.7 link	c.906+2328A>C		intron_variant	Intron 8 of 9	1	NM_182948.4	ENSP00000359719.3		P22694-2

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

65892

AN:

151554

Hom.:

15925

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.364

Gnomad FIN

AF:

0.513

Gnomad MID

AF:

0.434

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.466

GnomAD4 exome

AF:

0.546

AC:

452264

AN:

827722

Hom.:

125281

Cov.:

AF XY:

0.547

AC XY:

209236

AN XY:

382458

show subpopulations

African (AFR)

AF:

0.199

AC:

3131

AN:

15712

American (AMR)

AF:

0.381

AC:

374

AN:

982

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

2610

AN:

5128

East Asian (EAS)

AF:

0.369

AC:

1334

AN:

3614

South Asian (SAS)

AF:

0.367

AC:

6015

AN:

16374

European-Finnish (FIN)

AF:

0.551

AC:

152

AN:

276

Middle Eastern (MID)

AF:

0.471

AC:

758

AN:

1610

European-Non Finnish (NFE)

AF:

0.560

AC:

424034

AN:

756900

Other (OTH)

AF:

0.511

AC:

13856

AN:

27126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

9808

19617

29425

39234

49042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.434

AC:

65891

AN:

151670

Hom.:

15926

Cov.:

AF XY:

0.430

AC XY:

31841

AN XY:

74054

show subpopulations

African (AFR)

AF:

0.225

AC:

9330

AN:

41452

American (AMR)

AF:

0.410

AC:

6252

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

1766

AN:

3468

East Asian (EAS)

AF:

0.361

AC:

1865

AN:

5168

South Asian (SAS)

AF:

0.364

AC:

1750

AN:

4814

European-Finnish (FIN)

AF:

0.513

AC:

5402

AN:

10530

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38046

AN:

67682

Other (OTH)

AF:

0.463

AC:

975

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1748

3496

5245

6993

8741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.507

Hom.:

6996

Bravo

AF:

0.418

Asia WGS

AF:

0.356

AC:

1235

AN:

3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.6

(source)

DANN

Benign

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

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.

1-84205133-A-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over