chr1-84205133-A-C

Variant names:

• chr1-84205133-A-C
• rs1057738
• ENST00000370680.5:c.*643A>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001300916.2. 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.906+2328A>C		intron	N/A	NP_891993.1	P22694-2
	PRKACB	NM_001300916.2		c.*643A>C		3_prime_UTR	Exon 9 of 9	NP_001287845.1
	PRKACB	NM_001375581.1		c.*643A>C		3_prime_UTR	Exon 12 of 12	NP_001362510.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	ENST00000370680.5	TSL:1	c.*643A>C		3_prime_UTR	Exon 12 of 12	ENSP00000359714.1	B1APG3
	PRKACB	ENST00000370688.7	TSL:1	c.*643A>C		3_prime_UTR	Exon 9 of 9	ENSP00000359722.3	P22694-8
	PRKACB	ENST00000370685.7	TSL:1 MANE Select	c.906+2328A>C		intron	N/A	ENSP00000359719.3	P22694-2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65892 AN: 151554 Hom.: 15925 Cov.: 32

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.: 26 AF XY: 0.547 AC XY: 209236 AN XY: 382458

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

GnomAD4 genome AF: 0.434 AC: 65891 AN: 151670 Hom.: 15926 Cov.: 32 AF XY: 0.430 AC XY: 31841 AN XY: 74054

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.6
DANN	Benign	0.71
PhyloP100		0.61
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: rs1057738; hg19: chr1-84670816; COSMIC: COSV65759181; COSMIC: COSV65759181;