rs12060491

Variant names:

• chr1-66279669-A-G
• rs12060491
• NM_002600.4:c.634+13582A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-66279669-A-G
• chr1-66279669-A-T

Variant summary

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

The NM_002600.4(PDE4B):​c.634+13582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,184 control chromosomes in the GnomAD database, including 3,685 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 0.20 (3685 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• Publications: 6 publications found

Genes affected

PDE4B (HGNC:8781): (phosphodiesterase 4B) This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. The encoded protein regulates the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

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 (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002600.4. 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
	PDE4B	NM_002600.4	MANE Select	c.634+13582A>G		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.634+13582A>G		intron	N/A	NP_001032418.1
	PDE4B	NM_001037340.3		c.589+13582A>G		intron	N/A	NP_001032417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.634+13582A>G		intron	N/A	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.634+13582A>G		intron	N/A	ENSP00000332116.4
	PDE4B	ENST00000423207.6	TSL:1	c.589+13582A>G		intron	N/A	ENSP00000392947.2

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31167 AN: 152066 Hom.: 3678 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.205 AC: 31197 AN: 152184 Hom.: 3685 Cov.: 32 AF XY: 0.211 AC XY: 15718 AN XY: 74410

African (AFR) AF: 0.197 AC: 8185 AN: 41522

American (AMR) AF: 0.312 AC: 4760 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2135 AN: 5176

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4818

European-Finnish (FIN) AF: 0.165 AC: 1749 AN: 10598

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11384 AN: 68004

Other (OTH) AF: 0.208 AC: 440 AN: 2112

Alfa AF: 0.186 Hom.: 5295

Bravo AF: 0.211

Asia WGS AF: 0.389 AC: 1354 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	5.0
DANN	Benign	0.70
PhyloP100		0.57
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: rs12060491; hg19: chr1-66745352;