1-66274741-G-C

Position:

• chr1-66274741-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002600.4(PDE4B):​c.634+8654G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 152,260 control chromosomes in the GnomAD database, including 48 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 0.022 (48 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0219 (3333/152260) while in subpopulation AFR AF= 0.041 (1702/41558). AF 95% confidence interval is 0.0393. There are 48 homozygotes in gnomad4. There are 1609 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3333 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.634+8654G>C		intron_variant		ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.634+8654G>C		intron_variant		1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.634+8654G>C		intron_variant		1		ENSP00000332116.4
PDE4B	ENST00000423207.6	c.589+8654G>C		intron_variant		1		ENSP00000392947.2
PDE4B	ENST00000412480.6	c.358+8654G>C		intron_variant		4		ENSP00000397548.2

Frequencies

GnomAD3 genomes AF: 0.0218 AC: 3323 AN: 152142 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.00950

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.0129

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0191

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

GnomAD4 genome AF: 0.0219 AC: 3333 AN: 152260 Hom.: 48 Cov.: 32 AF XY: 0.0216 AC XY: 1609 AN XY: 74464

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.00950

Gnomad4 EAS AF: 0.00444

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.0129

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.00387 Hom.: 2

Bravo AF: 0.0252

Asia WGS AF: 0.0290 AC: 100 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.6
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs10493401; hg19: chr1-66740424;