1-66081326-T-C

Variant names:

• chr1-66081326-T-C
• rs6588186
• NM_002600.4:c.281+162491T>C

Variant summary

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

The NM_002600.4(PDE4B):​c.281+162491T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,970 control chromosomes in the GnomAD database, including 42,999 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 0.74 (42999 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.417
• Publications: 8 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.836 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.281+162491T>C		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.281+162491T>C		intron	N/A	NP_001032418.1
	PDE4B	NM_001037340.3		c.236+88184T>C		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.281+162491T>C		intron	N/A	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.281+162491T>C		intron	N/A	ENSP00000332116.4
	PDE4B	ENST00000423207.6	TSL:1	c.236+88184T>C		intron	N/A	ENSP00000392947.2

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112806 AN: 151852 Hom.: 42976 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.841

Gnomad OTH AF: 0.770

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

GnomAD4 genome AF: 0.743 AC: 112874 AN: 151970 Hom.: 42999 Cov.: 31 AF XY: 0.740 AC XY: 54949 AN XY: 74260

African (AFR) AF: 0.587 AC: 24305 AN: 41430

American (AMR) AF: 0.718 AC: 10933 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2741 AN: 3470

East Asian (EAS) AF: 0.599 AC: 3094 AN: 5162

South Asian (SAS) AF: 0.653 AC: 3143 AN: 4816

European-Finnish (FIN) AF: 0.841 AC: 8894 AN: 10572

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.841 AC: 57184 AN: 67970

Other (OTH) AF: 0.764 AC: 1611 AN: 2110

Alfa AF: 0.805 Hom.: 147044

Bravo AF: 0.729

Asia WGS AF: 0.613 AC: 2130 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.79
PhyloP100		0.42
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: rs6588186; hg19: chr1-66547009;