rs1318475

Variant names:

• chr1-65964509-G-C
• rs1318475
• NM_002600.4:c.281+45674G>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+45674G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,046 control chromosomes in the GnomAD database, including 31,702 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 0.64 (31702 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.281+45674G>C		intron_variant	Intron 3 of 16	ENST00000341517.9	NP_002591.2
PDE4B	NM_001037341.2	c.281+45674G>C		intron_variant	Intron 3 of 16		NP_001032418.1
PDE4B	NM_001297441.1	c.46+51149G>C		intron_variant	Intron 1 of 15		NP_001284370.1
PDE4B	NM_001297440.2	c.5+51153G>C		intron_variant	Intron 2 of 15		NP_001284369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.281+45674G>C		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.281+45674G>C		intron_variant	Intron 3 of 16	1		ENSP00000332116.4

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97889 AN: 151928 Hom.: 31673 Cov.: 32

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.575

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.644 AC: 97971 AN: 152046 Hom.: 31702 Cov.: 32 AF XY: 0.645 AC XY: 47946 AN XY: 74312

African (AFR) AF: 0.684 AC: 28359 AN: 41478

American (AMR) AF: 0.607 AC: 9262 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3470

East Asian (EAS) AF: 0.536 AC: 2774 AN: 5172

South Asian (SAS) AF: 0.575 AC: 2763 AN: 4806

European-Finnish (FIN) AF: 0.700 AC: 7386 AN: 10558

Middle Eastern (MID) AF: 0.551 AC: 161 AN: 292

European-Non Finnish (NFE) AF: 0.639 AC: 43427 AN: 67980

Other (OTH) AF: 0.625 AC: 1321 AN: 2114

Alfa AF: 0.648 Hom.: 3998

Bravo AF: 0.640

Asia WGS AF: 0.534 AC: 1855 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.1
DANN	Benign	0.74
PhyloP100		-0.032
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: rs1318475; hg19: chr1-66430192; COSMIC: COSV58470616;