chr6-135998083-A-G

Variant names:

• chr6-135998083-A-G
• rs17065195
• NM_018945.4:c.82+50559A>G

Variant summary

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

The NM_018945.4(PDE7B):​c.82+50559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,306 control chromosomes in the GnomAD database, including 557 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 0.049 (557 hom., cov: 32)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

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.82+50559A>G		intron	N/A	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.82+50559A>G		intron	N/A	ENSP00000310661.6	Q9NP56
	PDE7B-AS1	ENST00000626414.1	TSL:5	n.157-4946T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0488 AC: 7425 AN: 152188 Hom.: 547 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.0287

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00118

Gnomad OTH AF: 0.0416

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

GnomAD4 genome AF: 0.0490 AC: 7464 AN: 152306 Hom.: 557 Cov.: 32 AF XY: 0.0475 AC XY: 3541 AN XY: 74472

African (AFR) AF: 0.162 AC: 6744 AN: 41538

American (AMR) AF: 0.0191 AC: 293 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3472

East Asian (EAS) AF: 0.0283 AC: 147 AN: 5186

South Asian (SAS) AF: 0.0188 AC: 91 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68028

Other (OTH) AF: 0.0435 AC: 92 AN: 2114

Alfa AF: 0.0183 Hom.: 117

Bravo AF: 0.0544

Asia WGS AF: 0.0450 AC: 155 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.64
PhyloP100		0.14
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: rs17065195; hg19: chr6-136319221;