7-551426-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001164760.2(PRKAR1B):c.936C>T(p.Tyr312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000814 in 1,560,538 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (2 hom.)
• Consequence: PRKAR1B NM_001164760.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 7-551426-G-A is Benign according to our data. Variant chr7-551426-G-A is described in ClinVar as [Benign]. Clinvar id is 782256.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-551426-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00369 (562/152194) while in subpopulation AFR AF= 0.0124 (513/41502). AF 95% confidence interval is 0.0115. There are 4 homozygotes in gnomad4. There are 275 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 556 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKAR1B	NM_001164760.2	c.936C>T	p.Tyr312=	synonymous_variant	10/11	ENST00000537384.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKAR1B	ENST00000537384.6	c.936C>T	p.Tyr312=	synonymous_variant	10/11	5	NM_001164760.2	P1

Frequencies

GnomAD3 genomes AF: 0.00366 AC: 556 AN: 152076 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000883

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000975 AC: 164 AN: 168218 Hom.: 1 AF XY: 0.000747 AC XY: 67 AN XY: 89684

Gnomad AFR exome AF: 0.0121

Gnomad AMR exome AF: 0.000513

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000900

Gnomad SAS exome AF: 0.000254

Gnomad FIN exome AF: 0.0000632

Gnomad NFE exome AF: 0.0000600

Gnomad OTH exome AF: 0.000436

GnomAD4 exome AF: 0.000503 AC: 709 AN: 1408344 Hom.: 2 Cov.: 31 AF XY: 0.000457 AC XY: 318 AN XY: 695486

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.000716

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00487

Gnomad4 SAS exome AF: 0.000312

Gnomad4 FIN exome AF: 0.0000207

Gnomad4 NFE exome AF: 0.0000286

Gnomad4 OTH exome AF: 0.00105

GnomAD4 genome AF: 0.00369 AC: 562 AN: 152194 Hom.: 4 Cov.: 33 AF XY: 0.00370 AC XY: 275 AN XY: 74412

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000883

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00157 Hom.: 1

Bravo AF: 0.00389

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
Cadd	Benign	0.44
Dann	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs144431535; hg19: chr7-591063;