1-65907223-G-A

Variant names:

• chr1-65907223-G-A
• rs11208766
• NM_002600.4:c.-70-6022G>A

Variant summary

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

The NM_002600.4(PDE4B):​c.-70-6022G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,958 control chromosomes in the GnomAD database, including 17,482 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 (17482 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	NM_002600.4	MANE Select	c.-70-6022G>A		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.-70-6022G>A		intron	N/A	NP_001032418.1
	PDE4B	NM_001297440.2		c.-107-6022G>A		intron	N/A	NP_001284369.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.-70-6022G>A		intron	N/A	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.-70-6022G>A		intron	N/A	ENSP00000332116.4

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71989 AN: 151840 Hom.: 17450 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.474 AC: 72070 AN: 151958 Hom.: 17482 Cov.: 32 AF XY: 0.477 AC XY: 35462 AN XY: 74274

African (AFR) AF: 0.373 AC: 15444 AN: 41408

American (AMR) AF: 0.553 AC: 8433 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1871 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3052 AN: 5174

South Asian (SAS) AF: 0.664 AC: 3205 AN: 4828

European-Finnish (FIN) AF: 0.446 AC: 4715 AN: 10566

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.495 AC: 33631 AN: 67950

Other (OTH) AF: 0.496 AC: 1048 AN: 2112

Alfa AF: 0.479 Hom.: 3414

Bravo AF: 0.475

Asia WGS AF: 0.680 AC: 2361 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.097
DANN	Benign	0.23
PhyloP100		-0.73
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: rs11208766; hg19: chr1-66372906;