chr1-66372393-C-T

Variant names:

• chr1-66372393-C-T
• rs79722858
• NM_002600.4:c.1926C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_002600.4(PDE4B):​c.1926C>T​(p.Leu642Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,972 control chromosomes in the GnomAD database, including 128 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0084 (10 hom., cov: 32)
  • Exomes 𝑓: 0.010 (118 hom.)
• Consequence: PDE4B NM_002600.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.04
• Publications: 4 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 1-66372393-C-T is Benign according to our data. Variant chr1-66372393-C-T is described in ClinVar as Benign. ClinVar VariationId is 708064.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.04 with no splicing effect.
• BS2: High AC in GnomAd4 at 1272 AD gene.

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.1926C>T	p.Leu642Leu	synonymous	Exon 17 of 17	NP_002591.2
	PDE4B	NM_001037341.2		c.1926C>T	p.Leu642Leu	synonymous	Exon 17 of 17	NP_001032418.1	X5DNX5
	PDE4B	NM_001037340.3		c.1881C>T	p.Leu627Leu	synonymous	Exon 15 of 15	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.1926C>T	p.Leu642Leu	synonymous	Exon 17 of 17	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.1926C>T	p.Leu642Leu	synonymous	Exon 17 of 17	ENSP00000332116.4	Q07343-1
	PDE4B	ENST00000423207.6	TSL:1	c.1881C>T	p.Leu627Leu	synonymous	Exon 15 of 15	ENSP00000392947.2	Q07343-3

Frequencies

GnomAD3 genomes AF: 0.00836 AC: 1271 AN: 152118 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00188

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00853 AC: 2140 AN: 251018 AF XY: 0.00840

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00333

Gnomad ASJ exome AF: 0.0209

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0153

Gnomad NFE exome AF: 0.0118

Gnomad OTH exome AF: 0.00866

GnomAD4 exome AF: 0.0103 AC: 15049 AN: 1461736 Hom.: 118 Cov.: 31 AF XY: 0.0100 AC XY: 7297 AN XY: 727182

African (AFR) AF: 0.00134 AC: 45 AN: 33476

American (AMR) AF: 0.00349 AC: 156 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0215 AC: 563 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.00233 AC: 201 AN: 86256

European-Finnish (FIN) AF: 0.0169 AC: 903 AN: 53418

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5768

European-Non Finnish (NFE) AF: 0.0114 AC: 12687 AN: 1111892

Other (OTH) AF: 0.00803 AC: 485 AN: 60384

GnomAD4 genome AF: 0.00836 AC: 1272 AN: 152236 Hom.: 10 Cov.: 32 AF XY: 0.00832 AC XY: 619 AN XY: 74432

African (AFR) AF: 0.00188 AC: 78 AN: 41536

American (AMR) AF: 0.00314 AC: 48 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00373 AC: 18 AN: 4822

European-Finnish (FIN) AF: 0.0157 AC: 166 AN: 10588

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 876 AN: 68010

Other (OTH) AF: 0.00662 AC: 14 AN: 2116

Alfa AF: 0.0104 Hom.: 21

Bravo AF: 0.00686

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.00931

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.4
DANN	Benign	0.69
PhyloP100		3.0
Mutation Taster		=97/3	polymorphism

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: rs79722858; hg19: chr1-66838076; COSMIC: COSV100302927; COSMIC: COSV100302927;