chr1-65813442-A-G

Variant names:

• chr1-65813442-A-G
• rs4384209
• NM_002600.4:c.-71+20194A>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.-71+20194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.676 in 150,730 control chromosomes in the GnomAD database, including 35,627 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 0.68 (35627 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.-71+20194A>G		intron_variant	Intron 1 of 16	ENST00000341517.9	NP_002591.2
PDE4B	NM_001037341.2	c.-71+20812A>G		intron_variant	Intron 1 of 16		NP_001032418.1
PDE4B	NM_001297440.2	c.-108+20812A>G		intron_variant	Intron 1 of 15		NP_001284369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.-71+20194A>G		intron_variant	Intron 1 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.-71+20812A>G		intron_variant	Intron 1 of 16	1		ENSP00000332116.4

Frequencies

GnomAD3 genomes AF: 0.677 AC: 101915 AN: 150632 Hom.: 35630 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.751

Gnomad EAS AF: 0.345

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.689

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

GnomAD4 genome AF: 0.676 AC: 101939 AN: 150730 Hom.: 35627 Cov.: 31 AF XY: 0.672 AC XY: 49515 AN XY: 73654

African (AFR) AF: 0.529 AC: 21227 AN: 40142

American (AMR) AF: 0.624 AC: 9517 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2607 AN: 3472

East Asian (EAS) AF: 0.346 AC: 1789 AN: 5174

South Asian (SAS) AF: 0.616 AC: 2970 AN: 4824

European-Finnish (FIN) AF: 0.779 AC: 8256 AN: 10592

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.782 AC: 53187 AN: 67974

Other (OTH) AF: 0.685 AC: 1441 AN: 2104

Alfa AF: 0.744 Hom.: 172354

Bravo AF: 0.653

Asia WGS AF: 0.482 AC: 1678 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.59
PhyloP100		0.12
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: rs4384209; hg19: chr1-66279125;