chr1-66348173-G-A

Variant names:

• chr1-66348173-G-A
• rs10493402
• NM_002600.4:c.748-7354G>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.748-7354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0793 in 152,104 control chromosomes in the GnomAD database, including 1,280 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 0.079 (1280 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.665
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 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.748-7354G>A		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.748-7354G>A		intron	N/A	NP_001032418.1	X5DNX5
	PDE4B	NM_001037340.3		c.703-7354G>A		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.748-7354G>A		intron	N/A	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.748-7354G>A		intron	N/A	ENSP00000332116.4	Q07343-1
	PDE4B	ENST00000423207.6	TSL:1	c.703-7354G>A		intron	N/A	ENSP00000392947.2	Q07343-3

Frequencies

GnomAD3 genomes AF: 0.0791 AC: 12018 AN: 151986 Hom.: 1269 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0233

Gnomad SAS AF: 0.0844

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.00818

Gnomad OTH AF: 0.0756

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

GnomAD4 genome AF: 0.0793 AC: 12067 AN: 152104 Hom.: 1280 Cov.: 32 AF XY: 0.0788 AC XY: 5862 AN XY: 74376

African (AFR) AF: 0.236 AC: 9784 AN: 41430

American (AMR) AF: 0.0625 AC: 956 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3468

East Asian (EAS) AF: 0.0234 AC: 121 AN: 5182

South Asian (SAS) AF: 0.0842 AC: 406 AN: 4820

European-Finnish (FIN) AF: 0.00226 AC: 24 AN: 10608

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.00818 AC: 556 AN: 67988

Other (OTH) AF: 0.0748 AC: 158 AN: 2112

Alfa AF: 0.0440 Hom.: 888

Bravo AF: 0.0912

Asia WGS AF: 0.0800 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.45
DANN	Benign	0.80
PhyloP100		-0.67
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: rs10493402; hg19: chr1-66813856;