chr7-550023-C-G

Variant names:

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

Variant summary

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

The NM_002735.3(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_002735.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 11 publications found

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]

PRKAR1B Gene-Disease associations (from GenCC):

• Marbach-Schaaf neurodevelopmental syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• PRKAR1B-related neurodegenerative dementia with intermediate filaments

  Inheritance: AD 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002735.3. 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
	PRKAR1B	NM_001164760.2	MANE Select	c.*407G>C		3_prime_UTR	Exon 11 of 11	NP_001158232.1
	PRKAR1B	NM_001164758.2		c.*407G>C		3_prime_UTR	Exon 11 of 11	NP_001158230.1
	PRKAR1B	NM_001164759.1		c.*407G>C		3_prime_UTR	Exon 11 of 11	NP_001158231.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKAR1B	ENST00000537384.6	TSL:5 MANE Select	c.*407G>C		3_prime_UTR	Exon 11 of 11	ENSP00000440449.1
	PRKAR1B	ENST00000360274.8	TSL:1	c.*407G>C		3_prime_UTR	Exon 11 of 11	ENSP00000353415.4
	PRKAR1B	ENST00000403562.5	TSL:1	c.*407G>C		3_prime_UTR	Exon 11 of 11	ENSP00000385349.1

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

African (AFR) AF: 0.113 AC: 54 AN: 476

American (AMR) AF: 0.365 AC: 1121 AN: 3074

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 125 AN: 796

East Asian (EAS) AF: 0.132 AC: 119 AN: 902

South Asian (SAS) AF: 0.105 AC: 617 AN: 5902

European-Finnish (FIN) AF: 0.0767 AC: 132 AN: 1722

Middle Eastern (MID) AF: 0.185 AC: 23 AN: 124

European-Non Finnish (NFE) AF: 0.105 AC: 2559 AN: 24272

Other (OTH) AF: 0.124 AC: 255 AN: 2060

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

African (AFR) AF: 0.147 AC: 6107 AN: 41448

American (AMR) AF: 0.309 AC: 4713 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 585 AN: 3468

East Asian (EAS) AF: 0.143 AC: 735 AN: 5122

South Asian (SAS) AF: 0.112 AC: 538 AN: 4820

European-Finnish (FIN) AF: 0.0970 AC: 1029 AN: 10608

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8765 AN: 67974

Other (OTH) AF: 0.144 AC: 304 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.54
PhyloP100		-0.076
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: rs2763; hg19: chr7-589660;