1-66351329-G-C

Variant names:

• chr1-66351329-G-C
• rs10493403
• NM_002600.4:c.748-4198G>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.748-4198G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 152,232 control chromosomes in the GnomAD database, including 1,293 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 0.080 (1293 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 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.748-4198G>C		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.748-4198G>C		intron	N/A	NP_001032418.1	X5DNX5
	PDE4B	NM_001037340.3		c.703-4198G>C		intron	N/A	NP_001032417.1	Q07343-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.748-4198G>C		intron	N/A	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.748-4198G>C		intron	N/A	ENSP00000332116.4	Q07343-1
	PDE4B	ENST00000423207.6	TSL:1	c.703-4198G>C		intron	N/A	ENSP00000392947.2	Q07343-3

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12068 AN: 152114 Hom.: 1282 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0231

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00816

Gnomad OTH AF: 0.0761

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

GnomAD4 genome AF: 0.0796 AC: 12117 AN: 152232 Hom.: 1293 Cov.: 32 AF XY: 0.0790 AC XY: 5877 AN XY: 74416

African (AFR) AF: 0.237 AC: 9826 AN: 41502

American (AMR) AF: 0.0629 AC: 962 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3472

East Asian (EAS) AF: 0.0231 AC: 120 AN: 5190

South Asian (SAS) AF: 0.0847 AC: 409 AN: 4828

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10616

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00816 AC: 555 AN: 68012

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0437 Hom.: 84

Bravo AF: 0.0913

Asia WGS AF: 0.0800 AC: 276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		0.28
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10493403; hg19: chr1-66817012;