chr1-66093076-A-G

Variant names:

• chr1-66093076-A-G
• rs4655595
• NM_002600.4:c.282-154384A>G

Variant summary

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

The NM_002600.4(PDE4B):​c.282-154384A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,042 control chromosomes in the GnomAD database, including 1,643 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 (1643 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.299 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.282-154384A>G		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.282-154384A>G		intron	N/A	NP_001032418.1
	PDE4B	NM_001037340.3		c.236+99934A>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.282-154384A>G		intron	N/A	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.282-154384A>G		intron	N/A	ENSP00000332116.4
	PDE4B	ENST00000423207.6	TSL:1	c.236+99934A>G		intron	N/A	ENSP00000392947.2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19952 AN: 151922 Hom.: 1636 Cov.: 32

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0713

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.0596

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.148

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

GnomAD4 genome AF: 0.131 AC: 19992 AN: 152042 Hom.: 1643 Cov.: 32 AF XY: 0.133 AC XY: 9897 AN XY: 74314

African (AFR) AF: 0.170 AC: 7054 AN: 41476

American (AMR) AF: 0.137 AC: 2082 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 496 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1607 AN: 5150

South Asian (SAS) AF: 0.309 AC: 1489 AN: 4822

European-Finnish (FIN) AF: 0.0596 AC: 632 AN: 10606

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0913 AC: 6202 AN: 67952

Other (OTH) AF: 0.150 AC: 316 AN: 2110

Alfa AF: 0.112 Hom.: 4762

Bravo AF: 0.138

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.0
DANN	Benign	0.61
PhyloP100		0.31
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: rs4655595; hg19: chr1-66558759; COSMIC: COSV58471043; COSMIC: COSV58471043;