1-66330543-C-T

Variant names:

• chr1-66330543-C-T
• rs910694
• NM_002600.4:c.635-1965C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002600.4(PDE4B):​c.635-1965C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,108 control chromosomes in the GnomAD database, including 18,396 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 0.47 (18396 hom., cov: 33)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.903
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 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.635-1965C>T		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.635-1965C>T		intron	N/A	NP_001032418.1	X5DNX5
	PDE4B	NM_001037340.3		c.590-1965C>T		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.635-1965C>T		intron	N/A	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.635-1965C>T		intron	N/A	ENSP00000332116.4	Q07343-1
	PDE4B	ENST00000423207.6	TSL:1	c.590-1965C>T		intron	N/A	ENSP00000392947.2	Q07343-3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71354 AN: 151990 Hom.: 18395 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.469 AC: 71380 AN: 152108 Hom.: 18396 Cov.: 33 AF XY: 0.473 AC XY: 35148 AN XY: 74350

African (AFR) AF: 0.250 AC: 10358 AN: 41504

American (AMR) AF: 0.548 AC: 8373 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 2115 AN: 3468

East Asian (EAS) AF: 0.804 AC: 4164 AN: 5178

South Asian (SAS) AF: 0.527 AC: 2540 AN: 4820

European-Finnish (FIN) AF: 0.518 AC: 5464 AN: 10548

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.538 AC: 36567 AN: 67990

Other (OTH) AF: 0.491 AC: 1037 AN: 2110

Alfa AF: 0.380 Hom.: 1363

Bravo AF: 0.464

Asia WGS AF: 0.592 AC: 2056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.91
DANN	Benign	0.62
PhyloP100		-0.90
PromoterAI		0.030	Neutral
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: rs910694; hg19: chr1-66796226;