rs9376173

chr6-136038308-A-Cchr6-136038308-A-Gchr6-136038308-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000615259.4(PDE7B):c.18A>C(p.Arg6=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,294,150 control chromosomes in the GnomAD database, including 56,944 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 0.30 (7356 hom., cov: 32)
  • Exomes 𝑓: 0.29 (49588 hom.)
• Consequence: PDE7B ENST00000615259.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.534 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE7B	NM_018945.4	c.83-70423A>C		intron_variant		ENST00000308191.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE7B	ENST00000615259.4	c.18A>C	p.Arg6=	synonymous_variant	1/12	1
PDE7B	ENST00000308191.11	c.83-70423A>C		intron_variant		1	NM_018945.4	P1
PDE7B-AS1	ENST00000576956.3	n.617-3013T>G		intron_variant, non_coding_transcript_variant		5
PDE7B-AS1	ENST00000626414.1	n.74-25595T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45412 AN: 151876 Hom.: 7351 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.320

GnomAD3 exomes AF: 0.332 AC: 45923 AN: 138286 Hom.: 8687 AF XY: 0.312 AC XY: 23412 AN XY: 74940

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.534

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.335

GnomAD4 exome AF: 0.289 AC: 329917 AN: 1142156 Hom.: 49588 Cov.: 35 AF XY: 0.284 AC XY: 159088 AN XY: 560610

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.541

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.392

Gnomad4 NFE exome AF: 0.288

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.299 AC: 45443 AN: 151994 Hom.: 7356 Cov.: 32 AF XY: 0.308 AC XY: 22839 AN XY: 74258

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.319

Alfa AF: 0.292 Hom.: 9504

Bravo AF: 0.306

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	13
Dann	Benign	0.64

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: rs9376173; hg19: chr6-136359446; COSMIC: COSV57499665; COSMIC: COSV57499665;