rs11208756

Variant names:

• chr1-65803628-T-C
• rs11208756
• NM_002600.4:c.-71+10380T>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.-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 NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• Publications: 7 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=-0.84).
• 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 rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.-71+10380T>C		intron_variant	Intron 1 of 16	ENST00000341517.9	NP_002591.2
PDE4B	NM_001037341.2	c.-71+10998T>C		intron_variant	Intron 1 of 16		NP_001032418.1
PDE4B	NM_001297440.2	c.-108+10998T>C		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+10380T>C		intron_variant	Intron 1 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.-71+10998T>C		intron_variant	Intron 1 of 16	1		ENSP00000332116.4

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

African (AFR) AF: 0.400 AC: 16559 AN: 41422

American (AMR) AF: 0.106 AC: 1616 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1098 AN: 5184

South Asian (SAS) AF: 0.164 AC: 790 AN: 4816

European-Finnish (FIN) AF: 0.0559 AC: 592 AN: 10584

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.0839 AC: 5706 AN: 67986

Other (OTH) AF: 0.142 AC: 299 AN: 2112

Alfa AF: 0.112 Hom.: 2561

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
PhyloP100		0.58
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: rs11208756; hg19: chr1-66269311;