rs7546625

Variant names:

• chr1-84086923-G-A
• rs7546625
• ENST00000370689.6:c.46+8552G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-84086923-G-A
• chr1-84086923-G-T

Variant summary

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

The ENST00000370689.6(PRKACB):​c.46+8552G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,130 control chromosomes in the GnomAD database, including 1,637 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 0.13 (1637 hom., cov: 33)
• Consequence: PRKACB ENST00000370689.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 6 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]

TXN2P1 (HGNC:54554): (TXN2 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000370689.6. 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_002731.4		c.46+8552G>A		intron	N/A	NP_002722.1
	PRKACB	NM_001375576.1		c.46+8552G>A		intron	N/A	NP_001362505.1
	PRKACB	NM_207578.3		c.46+8552G>A		intron	N/A	NP_997461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACB	ENST00000370689.6	TSL:1	c.46+8552G>A		intron	N/A	ENSP00000359723.2
	PRKACB	ENST00000370688.7	TSL:1	c.46+8552G>A		intron	N/A	ENSP00000359722.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19200 AN: 152012 Hom.: 1636 Cov.: 33

Gnomad AFR AF: 0.0364

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0797

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19204 AN: 152130 Hom.: 1637 Cov.: 33 AF XY: 0.122 AC XY: 9083 AN XY: 74366

African (AFR) AF: 0.0364 AC: 1511 AN: 41516

American (AMR) AF: 0.141 AC: 2156 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 546 AN: 3470

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5170

South Asian (SAS) AF: 0.0796 AC: 384 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10554

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12757 AN: 67982

Other (OTH) AF: 0.139 AC: 294 AN: 2112

Alfa AF: 0.162 Hom.: 6239

Bravo AF: 0.122

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.2
DANN	Benign	0.77
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7546625; hg19: chr1-84552606;