rs600674

Variant names:

• chr1-84235568-T-C
• rs600674
• NM_182948.4:c.*263T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 12 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182948.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	NM_182948.4	MANE Select	c.*263T>C		3_prime_UTR	Exon 10 of 10	NP_891993.1
	PRKACB	NM_001242857.3		c.*263T>C		3_prime_UTR	Exon 13 of 13	NP_001229786.1
	PRKACB	NM_001242860.3		c.*263T>C		3_prime_UTR	Exon 13 of 13	NP_001229789.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	ENST00000370685.7	TSL:1 MANE Select	c.*263T>C		3_prime_UTR	Exon 10 of 10	ENSP00000359719.3
	PRKACB	ENST00000614872.4	TSL:1	c.*263T>C		3_prime_UTR	Exon 13 of 13	ENSP00000479722.1
	PRKACB	ENST00000370689.6	TSL:1	c.*263T>C		3_prime_UTR	Exon 10 of 10	ENSP00000359723.2

Frequencies

GnomAD3 genomes AF: 0.812 AC: 123557 AN: 152072 Hom.: 50292 Cov.: 32

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.: 3 AF XY: 0.796 AC XY: 82916 AN XY: 104108

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

GnomAD4 genome AF: 0.812 AC: 123640 AN: 152190 Hom.: 50334 Cov.: 32 AF XY: 0.813 AC XY: 60508 AN XY: 74418

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.5
DANN	Benign	0.73
PhyloP100		0.047
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs600674; hg19: chr1-84701251;