rs11208756

Positions:

• chr1-65803628-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000341517.9(PDE4B):​c.-71+10380T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,058 control chromosomes in the GnomAD database, including 3,993 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 0.18 (3993 hom., cov: 32)
• Consequence: PDE4B ENST00000341517.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.-71+10380T>C		intron_variant		ENST00000341517.9	NP_002591.2
PDE4B	NM_001037341.2	c.-71+10998T>C		intron_variant			NP_001032418.1
PDE4B	NM_001297440.2	c.-108+10998T>C		intron_variant			NP_001284369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.-71+10380T>C		intron_variant		1	NM_002600.4	ENSP00000342637	A1
PDE4B	ENST00000329654.8	c.-71+10998T>C		intron_variant		1		ENSP00000332116	A1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27310 AN: 151940 Hom.: 3988 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0559

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.180 AC: 27357 AN: 152058 Hom.: 3993 Cov.: 32 AF XY: 0.177 AC XY: 13151 AN XY: 74360

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0559

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.142

Alfa AF: 0.101 Hom.: 1400

Bravo AF: 0.193

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11208756; hg19: chr1-66269311;