chr1-66118774-T-C

Variant names:

• chr1-66118774-T-C
• rs7412571
• NM_002600.4:c.282-128686T>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.282-128686T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 152,044 control chromosomes in the GnomAD database, including 14,674 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 0.42 (14674 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.302
• Publications: 9 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.494 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.282-128686T>C		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.282-128686T>C		intron	N/A	NP_001032418.1	X5DNX5
	PDE4B	NM_001037340.3		c.236+125632T>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.282-128686T>C		intron	N/A	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.282-128686T>C		intron	N/A	ENSP00000332116.4	Q07343-1
	PDE4B	ENST00000423207.6	TSL:1	c.236+125632T>C		intron	N/A	ENSP00000392947.2	Q07343-3

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63813 AN: 151926 Hom.: 14669 Cov.: 31

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.420 AC: 63818 AN: 152044 Hom.: 14674 Cov.: 31 AF XY: 0.423 AC XY: 31402 AN XY: 74298

African (AFR) AF: 0.244 AC: 10127 AN: 41470

American (AMR) AF: 0.474 AC: 7238 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1369 AN: 3468

East Asian (EAS) AF: 0.369 AC: 1909 AN: 5174

South Asian (SAS) AF: 0.326 AC: 1573 AN: 4818

European-Finnish (FIN) AF: 0.594 AC: 6272 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.499 AC: 33907 AN: 67960

Other (OTH) AF: 0.418 AC: 883 AN: 2114

Alfa AF: 0.453 Hom.: 2248

Bravo AF: 0.404

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.72
PhyloP100		0.30
Mutation Taster		=100/0	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: rs7412571; hg19: chr1-66584457;