rs9376173

Variant names:

• chr6-136038308-A-C
• rs9376173
• ENST00000615259.4:c.18A>C
• PDE7B p.Arg6Arg

Your query was ambiguous. Multiple possible variants found:

• chr6-136038308-A-C
• chr6-136038308-A-G
• chr6-136038308-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000615259.4(PDE7B):​c.18A>C​(p.Arg6Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,294,150 control chromosomes in the GnomAD database, including 56,944 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 0.30 (7356 hom., cov: 32)
  • Exomes 𝑓: 0.29 (49588 hom.)
• Consequence: PDE7B ENST00000615259.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.534 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615259.4. 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.83-70423A>C		intron	N/A	NP_061818.1	Q9NP56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE7B	ENST00000615259.4	TSL:1	c.18A>C	p.Arg6Arg	synonymous	Exon 1 of 12	ENSP00000482117.1	A1E5M1
	PDE7B	ENST00000308191.11	TSL:1 MANE Select	c.83-70423A>C		intron	N/A	ENSP00000310661.6	Q9NP56
	PDE7B-AS1	ENST00000576956.3	TSL:5	n.617-3013T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45412 AN: 151876 Hom.: 7351 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.320

GnomAD2 exomes AF: 0.332 AC: 45923 AN: 138286 AF XY: 0.312

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.280

Gnomad EAS exome AF: 0.534

Gnomad FIN exome AF: 0.395

Gnomad NFE exome AF: 0.294

Gnomad OTH exome AF: 0.335

GnomAD4 exome AF: 0.289 AC: 329917 AN: 1142156 Hom.: 49588 Cov.: 35 AF XY: 0.284 AC XY: 159088 AN XY: 560610

African (AFR) AF: 0.222 AC: 5427 AN: 24466

American (AMR) AF: 0.495 AC: 14072 AN: 28428

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 4538 AN: 16000

East Asian (EAS) AF: 0.541 AC: 7154 AN: 13232

South Asian (SAS) AF: 0.176 AC: 13539 AN: 77086

European-Finnish (FIN) AF: 0.392 AC: 5521 AN: 14074

Middle Eastern (MID) AF: 0.297 AC: 1310 AN: 4410

European-Non Finnish (NFE) AF: 0.288 AC: 266125 AN: 922674

Other (OTH) AF: 0.293 AC: 12231 AN: 41786

GnomAD4 genome AF: 0.299 AC: 45443 AN: 151994 Hom.: 7356 Cov.: 32 AF XY: 0.308 AC XY: 22839 AN XY: 74258

African (AFR) AF: 0.227 AC: 9433 AN: 41474

American (AMR) AF: 0.409 AC: 6252 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3472

East Asian (EAS) AF: 0.535 AC: 2741 AN: 5122

South Asian (SAS) AF: 0.184 AC: 886 AN: 4826

European-Finnish (FIN) AF: 0.412 AC: 4338 AN: 10532

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19656 AN: 67972

Other (OTH) AF: 0.319 AC: 675 AN: 2114

Alfa AF: 0.296 Hom.: 22491

Bravo AF: 0.306

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.64
PhyloP100		-0.53
PromoterAI		-0.067	Neutral
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

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

Other links and lift over

dbSNP: rs9376173;

hg19: chr6-136359446;

COSMIC: COSV57499665;

COSMIC: COSV57499665;