7-550023-C-G

Variant names:

• chr7-550023-C-G
• rs2763
• NM_001164760.2:c.*407G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164760.2(PRKAR1B):​c.*407G>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 0.146 in 191,342 control chromosomes in the GnomAD database, including 2,480 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 0.15 (2044 hom., cov: 32)
  • Exomes 𝑓: 0.13 (436 hom.)
• Consequence: PRKAR1B NM_001164760.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760

Genes affected

PRKAR1B (HGNC:9390): (protein kinase cAMP-dependent type I regulatory subunit beta) The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAR1B	NM_001164760.2	c.*407G>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000537384.6	NP_001158232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAR1B	ENST00000537384	c.*407G>C		3_prime_UTR_variant	Exon 11 of 11	5	NM_001164760.2	ENSP00000440449.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22954 AN: 151894 Hom.: 2042 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.146

GnomAD4 exome AF: 0.127 AC: 5005 AN: 39328 Hom.: 436 Cov.: 0 AF XY: 0.126 AC XY: 2607 AN XY: 20638

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0767

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.151 AC: 22979 AN: 152014 Hom.: 2044 Cov.: 32 AF XY: 0.153 AC XY: 11366 AN XY: 74318

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0293 Hom.: 29

Bravo AF: 0.168

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs2763; hg19: chr7-589660;