rs138283749

Variant names:

• chr6-136173836-A-G
• rs138283749
• NM_018945.4:c.751A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_018945.4(PDE7B):​c.751A>G​(p.Ile251Val) variant causes a missense change. The variant allele was found at a frequency of 0.000026 in 1,612,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: PDE7B NM_018945.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16
• Publications: 2 publications found

Genes affected

PDE7B (HGNC:8792): (phosphodiesterase 7B) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a cAMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family.[provided by RefSeq, Apr 2009]

PDE7B-AS1 (HGNC:56334): (PDE7B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05521539).
• BS2: High AC in GnomAd4 at 24 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018945.4. 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
	PDE7B	NM_018945.4	MANE Select	c.751A>G	p.Ile251Val	missense	Exon 9 of 13	NP_061818.1	Q9NP56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE7B	ENST00000308191.11	TSL:1 MANE Select	c.751A>G	p.Ile251Val	missense	Exon 9 of 13	ENSP00000310661.6	Q9NP56
	PDE7B	ENST00000615259.4	TSL:1	c.907A>G	p.Ile303Val	missense	Exon 8 of 12	ENSP00000482117.1	A1E5M1
	PDE7B-AS1	ENST00000417643.5	TSL:5	n.59-11488T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000279 AC: 7 AN: 250804 AF XY: 0.0000295

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1460744 Hom.: 0 Cov.: 29 AF XY: 0.00000550 AC XY: 4 AN XY: 726752

African (AFR) AF: 0.000449 AC: 15 AN: 33418

American (AMR) AF: 0.0000672 AC: 3 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111156

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152090 Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10 AN XY: 74282

African (AFR) AF: 0.000531 AC: 22 AN: 41398

American (AMR) AF: 0.000131 AC: 2 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000263 Hom.: 0

Bravo AF: 0.000185

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	15
DANN	Benign	0.75
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.15	N
PhyloP100		5.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.18
Sift	Benign	0.90	T
Sift4G	Benign	0.98	T
Polyphen		0.0020	B
Vest4		0.22
MVP		0.26
MPC		0.27
ClinPred		0.081	T
GERP RS		1.8
Varity_R		0.041
gMVP		0.20
Mutation Taster		=89/11	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: rs138283749; hg19: chr6-136494974;