rs10782824

Variant names:

• chr1-84204901-T-A
• rs10782824
• ENST00000370680.5:c.*411T>A

Variant summary

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

The ENST00000370680.5(PRKACB):​c.*411T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 978,266 control chromosomes in the GnomAD database, including 145,265 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 0.49 (18730 hom., cov: 32)
  • Exomes 𝑓: 0.55 (126535 hom.)
• Consequence: PRKACB ENST00000370680.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370680.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	NM_182948.4	MANE Select	c.906+2096T>A		intron	N/A	NP_891993.1
	PRKACB	NM_001300916.2		c.*411T>A		3_prime_UTR	Exon 9 of 9	NP_001287845.1
	PRKACB	NM_001375581.1		c.*411T>A		3_prime_UTR	Exon 12 of 12	NP_001362510.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	ENST00000370680.5	TSL:1	c.*411T>A		3_prime_UTR	Exon 12 of 12	ENSP00000359714.1
	PRKACB	ENST00000370688.7	TSL:1	c.*411T>A		3_prime_UTR	Exon 9 of 9	ENSP00000359722.3
	PRKACB	ENST00000370685.7	TSL:1 MANE Select	c.906+2096T>A		intron	N/A	ENSP00000359719.3

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74139 AN: 151512 Hom.: 18699 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.551 AC: 455762 AN: 826636 Hom.: 126535 Cov.: 23 AF XY: 0.551 AC XY: 210654 AN XY: 381986

African (AFR) AF: 0.394 AC: 6180 AN: 15692

American (AMR) AF: 0.388 AC: 402 AN: 1036

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 2655 AN: 5152

East Asian (EAS) AF: 0.377 AC: 1378 AN: 3660

South Asian (SAS) AF: 0.389 AC: 6363 AN: 16348

European-Finnish (FIN) AF: 0.559 AC: 180 AN: 322

Middle Eastern (MID) AF: 0.487 AC: 788 AN: 1618

European-Non Finnish (NFE) AF: 0.561 AC: 423554 AN: 755654

Other (OTH) AF: 0.525 AC: 14262 AN: 27154

GnomAD4 genome AF: 0.489 AC: 74200 AN: 151630 Hom.: 18730 Cov.: 32 AF XY: 0.484 AC XY: 35870 AN XY: 74076

African (AFR) AF: 0.413 AC: 17093 AN: 41376

American (AMR) AF: 0.426 AC: 6498 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3470

East Asian (EAS) AF: 0.367 AC: 1897 AN: 5166

South Asian (SAS) AF: 0.385 AC: 1858 AN: 4832

European-Finnish (FIN) AF: 0.512 AC: 5394 AN: 10540

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38110 AN: 67696

Other (OTH) AF: 0.498 AC: 1050 AN: 2110

Alfa AF: 0.528 Hom.: 2652

Bravo AF: 0.480

Asia WGS AF: 0.384 AC: 1327 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.46
PhyloP100		-0.17
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: rs10782824; hg19: chr1-84670584; COSMIC: COSV65759178; COSMIC: COSV65759178;