dbSNP rs600674: PRKACB:c.*263T>C (chr1-84235568-T-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_182948.4(PRKACB):c.*263T>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 0.807 in 353,676 control chromosomes in the GnomAD database, including 115,096 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 0.81 ( 50334 hom., cov: 32)

Exomes 𝑓: 0.80 ( 64762 hom. )

Consequence

PRKACB
NM_182948.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0470

Publications

12 publications found

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 Gene-Disease associations (from GenCC):

cardioacrofacial dysplasia 2
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
Ellis-van Creveld syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PRKACB 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=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_182948.4 link	c.*263T>C		3_prime_UTR_variant	Exon 10 of 10	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.*263T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_182948.4	ENSP00000359719.3		P22694-2

Frequencies

GnomAD3 genomes

AF:

0.812

AC:

123557

AN:

152072

Hom.:

50292

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.820

Gnomad ASJ

AF:

0.806

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.693

Gnomad FIN

AF:

0.858

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.822

GnomAD4 exome

AF:

0.802

AC:

161616

AN:

201486

Hom.:

64762

Cov.:

AF XY:

0.796

AC XY:

82916

AN XY:

104108

show subpopulations

African (AFR)

AF:

0.836

AC:

4746

AN:

5678

American (AMR)

AF:

0.800

AC:

5280

AN:

6596

Ashkenazi Jewish (ASJ)

AF:

0.809

AC:

5514

AN:

6820

East Asian (EAS)

AF:

0.845

AC:

10399

AN:

12302

South Asian (SAS)

AF:

0.704

AC:

12091

AN:

17166

European-Finnish (FIN)

AF:

0.848

AC:

10074

AN:

11886

Middle Eastern (MID)

AF:

0.761

AC:

755

AN:

992

European-Non Finnish (NFE)

AF:

0.804

AC:

102526

AN:

127470

Other (OTH)

AF:

0.814

AC:

10231

AN:

12576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1555

3110

4664

6219

7774

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.812

AC:

123640

AN:

152190

Hom.:

50334

Cov.:

AF XY:

0.813

AC XY:

60508

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.837

AC:

34725

AN:

41508

American (AMR)

AF:

0.820

AC:

12530

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.806

AC:

2797

AN:

3472

East Asian (EAS)

AF:

0.783

AC:

4051

AN:

5174

South Asian (SAS)

AF:

0.691

AC:

3334

AN:

4824

European-Finnish (FIN)

AF:

0.858

AC:

9094

AN:

10604

Middle Eastern (MID)

AF:

0.755

AC:

222

AN:

294

European-Non Finnish (NFE)

AF:

0.802

AC:

54518

AN:

68004

Other (OTH)

AF:

0.813

AC:

1719

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1195

2390

3584

4779

5974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.807

Hom.:

64008

Bravo

AF:

0.814

Asia WGS

AF:

0.730

AC:

2539

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.5

(source)

DANN

Benign

0.73

PhyloP100

0.047

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over