rs10493389

Variant names:

• chr1-65845182-T-C
• rs10493389
• NM_002600.4:c.-71+51934T>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+51934T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,200 control chromosomes in the GnomAD database, including 1,087 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 0.11 (1087 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	NM_002600.4	MANE Select	c.-71+51934T>C		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.-71+52552T>C		intron	N/A	NP_001032418.1	X5DNX5
	PDE4B	NM_001297440.2		c.-108+52552T>C		intron	N/A	NP_001284369.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.-71+51934T>C		intron	N/A	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.-71+52552T>C		intron	N/A	ENSP00000332116.4	Q07343-1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17065 AN: 152082 Hom.: 1086 Cov.: 32

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.0891

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0838

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.112 AC: 17062 AN: 152200 Hom.: 1087 Cov.: 32 AF XY: 0.113 AC XY: 8375 AN XY: 74398

African (AFR) AF: 0.0688 AC: 2856 AN: 41538

American (AMR) AF: 0.0890 AC: 1361 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3472

East Asian (EAS) AF: 0.0834 AC: 432 AN: 5178

South Asian (SAS) AF: 0.125 AC: 604 AN: 4822

European-Finnish (FIN) AF: 0.130 AC: 1382 AN: 10596

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9381 AN: 67990

Other (OTH) AF: 0.115 AC: 243 AN: 2116

Alfa AF: 0.128 Hom.: 4362

Bravo AF: 0.107

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.3
DANN	Benign	0.77
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10493389;

hg19: chr1-66310865;