rs487278

Variant names:

• chr6-136180690-G-A
• rs487278
• NM_018945.4:c.949-537G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-136180690-G-A
• chr6-136180690-G-T

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NM_018945.4(PDE7B):c.949-537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The gene PDE7B is a tumor suppressor gene (CancerMine: 3 TSG, 1 oncogene citations). The gene PDE7B is a known oncogene (CancerMine: 3 TSG, 1 oncogene citations). The variant allele was found at a cumulative frequency of 0.49 (AC=74,560) in the gnomAD database across 152,156 control chromosomes, including 20,970 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.668. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (20970 hom., cov: 33)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.345
• Publications: 5 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): ()

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.668 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_018945.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PDE7B NM_018945.4	MANE Select	c.949-537G>A	intron	Intron 10 of 12	Prot: NP_061818.1 UniProt:

PDE7B NM_018945.4

MANE Select

HGVSc / HGVSpc.949-537G>A

Exon rankIntron 10 of 12

intron

Prot: NP_061818.1UniProt: Q9NP56

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PDE7B ENST00000308191.11	TSL:1MANE Select	c.949-537G>A	intron	Intron 10 of 12	Prot: ENSP00000310661.6 UniProt:
	PDE7B ENST00000615259.4	TSL:1	c.1105-537G>A	intron	Intron 9 of 11	Prot: ENSP00000482117.1 UniProt:
	PDE7B-AS1 ENST00000417643.5	TSL:5	n.59-18342C>T	intron	Intron 1 of 7	Prot:

PDE7B ENST00000308191.11

TSL:1MANE Select

HGVSc / HGVSpc.949-537G>A

Exon rankIntron 10 of 12

intron

Prot: ENSP00000310661.6UniProt: Q9NP56

PDE7B ENST00000615259.4

TSL:1

HGVSc / HGVSpc.1105-537G>A

Exon rankIntron 9 of 11

intron

Prot: ENSP00000482117.1UniProt: A0A087WYV0

PDE7B-AS1 ENST00000417643.5

TSL:5

HGVSc / HGVSpn.59-18342C>T

Exon rankIntron 1 of 7

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.491	AC:74575	Hom:20982	AN:152038	Cov:33
GnomAD4 genome	AF: 0.490	AC:74560	Hom:20970	AN:152156	Cov:33
TOPMed (Bravo)	AF: 0.473	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.564	AC:143075	Hom:43036	AN:253682	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.538	AC:1260	Hom:363	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.650	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.667	AC:200	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.585	AC:2036	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.619	AC:4477	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.636	AC:112	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.538	AC:66016	Hom:17730	AN:122818	Cov:
Turkish Variome	AF: 0.697	AC:1077	Hom:382	AN:1546	Cov:
UK10K	AF: 0.643	AC:4866	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.623	AC:5580	Hom:1763	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	2.7
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.90
DANN	Benign	0.33
GPN-Star LLR	N/A	-0.74
GPN-Star score	N/A	0.74
Mutation Taster	N/A	100/0	polymorphism (auto)
PhyloP100	Benign	-0.34

Showing 8 of 8 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs487278;

hg19: chr6-136501828;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar