1-66311907-A-T

Variant names:

• chr1-66311907-A-T
• rs1040716
• NM_002600.4:c.635-20601A>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.635-20601A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,032 control chromosomes in the GnomAD database, including 12,918 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 0.38 (12918 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 7 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.635-20601A>T		intron_variant	Intron 7 of 16	ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.635-20601A>T		intron_variant	Intron 7 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.635-20601A>T		intron_variant	Intron 7 of 16	1		ENSP00000332116.4
PDE4B	ENST00000423207.6	c.590-20601A>T		intron_variant	Intron 5 of 14	1		ENSP00000392947.2
PDE4B	ENST00000412480.6	c.359-20601A>T		intron_variant	Intron 5 of 5	4		ENSP00000397548.2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57442 AN: 151914 Hom.: 12922 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.378 AC: 57444 AN: 152032 Hom.: 12918 Cov.: 32 AF XY: 0.383 AC XY: 28439 AN XY: 74310

African (AFR) AF: 0.141 AC: 5862 AN: 41498

American (AMR) AF: 0.462 AC: 7057 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 1895 AN: 3468

East Asian (EAS) AF: 0.804 AC: 4160 AN: 5172

South Asian (SAS) AF: 0.515 AC: 2479 AN: 4818

European-Finnish (FIN) AF: 0.397 AC: 4187 AN: 10544

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30253 AN: 67950

Other (OTH) AF: 0.401 AC: 843 AN: 2104

Alfa AF: 0.393 Hom.: 1768

Bravo AF: 0.375

Asia WGS AF: 0.582 AC: 2021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.7
DANN	Benign	0.86
PhyloP100		0.030
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: rs1040716; hg19: chr1-66777590;