6-136187261-T-C

Variant names:

• chr6-136187261-T-C
• rs3734548
• NM_018945.4:c.1126+145T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018945.4(PDE7B):​c.1126+145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 589,298 control chromosomes in the GnomAD database, including 16,084 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 0.24 (11807 hom., cov: 32)
  • Exomes 𝑓: 0.064 (4277 hom.)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.1126+145T>C		intron_variant	Intron 12 of 12	ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.1126+145T>C		intron_variant	Intron 12 of 12	1	NM_018945.4	ENSP00000310661.6

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35763 AN: 152106 Hom.: 11750 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.0643 AC: 28118 AN: 437076 Hom.: 4277 AF XY: 0.0632 AC XY: 14674 AN XY: 232030

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.0708

Gnomad4 ASJ exome AF: 0.0301

Gnomad4 EAS exome AF: 0.195

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0355

Gnomad4 NFE exome AF: 0.0190

Gnomad4 OTH exome AF: 0.0899

GnomAD4 genome AF: 0.236 AC: 35887 AN: 152222 Hom.: 11807 Cov.: 32 AF XY: 0.231 AC XY: 17168 AN XY: 74426

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.203

Alfa AF: 0.144 Hom.: 1027

Bravo AF: 0.264

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.60

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: rs3734548; hg19: chr6-136508399;