6-136183898-A-C

Variant names:

• chr6-136183898-A-C
• rs560713
• NM_018945.4:c.1045+2575A>C

Variant summary

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

The NM_018945.4(PDE7B):​c.1045+2575A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 151,974 control chromosomes in the GnomAD database, including 45,039 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 0.76 (45039 hom., cov: 30)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 9 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 = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.1045+2575A>C		intron_variant	Intron 11 of 12	ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.1045+2575A>C		intron_variant	Intron 11 of 12	1	NM_018945.4	ENSP00000310661.6

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115500 AN: 151858 Hom.: 44986 Cov.: 30

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.761 AC: 115614 AN: 151974 Hom.: 45039 Cov.: 30 AF XY: 0.763 AC XY: 56686 AN XY: 74266

African (AFR) AF: 0.943 AC: 39153 AN: 41506

American (AMR) AF: 0.742 AC: 11319 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.681 AC: 2364 AN: 3472

East Asian (EAS) AF: 0.782 AC: 4014 AN: 5136

South Asian (SAS) AF: 0.762 AC: 3668 AN: 4812

European-Finnish (FIN) AF: 0.705 AC: 7437 AN: 10554

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45346 AN: 67930

Other (OTH) AF: 0.755 AC: 1593 AN: 2110

Alfa AF: 0.704 Hom.: 32436

Bravo AF: 0.772

Asia WGS AF: 0.810 AC: 2817 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.76
PhyloP100		-0.092
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: rs560713; hg19: chr6-136505036;