rs2327672

Variant names:

• chr6-135907081-G-A
• rs2327672
• NM_018945.4:c.22-40383G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018945.4(PDE7B):​c.22-40383G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 143,054 control chromosomes in the GnomAD database, including 2,092 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 0.17 (2092 hom., cov: 29)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0810
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.22-40383G>A		intron_variant	Intron 1 of 12	ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.22-40383G>A		intron_variant	Intron 1 of 12	1	NM_018945.4	ENSP00000310661.6

Frequencies

GnomAD3 genomes AF: 0.165 AC: 23645 AN: 142938 Hom.: 2086 Cov.: 29

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.0716

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.165 AC: 23667 AN: 143054 Hom.: 2092 Cov.: 29 AF XY: 0.167 AC XY: 11677 AN XY: 69948

African (AFR) AF: 0.174 AC: 6082 AN: 34904

American (AMR) AF: 0.240 AC: 3595 AN: 14980

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 455 AN: 3416

East Asian (EAS) AF: 0.337 AC: 1723 AN: 5116

South Asian (SAS) AF: 0.267 AC: 1226 AN: 4584

European-Finnish (FIN) AF: 0.0690 AC: 700 AN: 10152

Middle Eastern (MID) AF: 0.112 AC: 32 AN: 286

European-Non Finnish (NFE) AF: 0.142 AC: 9482 AN: 66702

Other (OTH) AF: 0.153 AC: 307 AN: 2006

Alfa AF: 0.153 Hom.: 4157

Bravo AF: 0.168

Asia WGS AF: 0.293 AC: 1016 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.49
PhyloP100		0.081
Mutation Taster		=100/0	polymorphism (auto)

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: rs2327672; hg19: chr6-136228219;