6-136190334-A-G

Position:

• chr6-136190334-A-G

Variant summary

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

The NM_018945.4(PDE7B):​c.1127-1280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,116 control chromosomes in the GnomAD database, including 11,827 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 (11827 hom., cov: 32)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.390

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.1127-1280A>G		intron_variant		ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.1127-1280A>G		intron_variant		1	NM_018945.4	ENSP00000310661.6

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35795 AN: 151998 Hom.: 11770 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0373

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.236 AC: 35920 AN: 152116 Hom.: 11827 Cov.: 32 AF XY: 0.231 AC XY: 17189 AN XY: 74364

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0373

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.204

Alfa AF: 0.160 Hom.: 1149

Bravo AF: 0.264

Asia WGS AF: 0.217 AC: 754 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	10
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3799396; hg19: chr6-136511472;