6-136173871-T-C

Variant names:

• chr6-136173871-T-C
• rs73555079
• NM_018945.4:c.786T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018945.4(PDE7B):​c.786T>C​(p.His262His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,611,710 control chromosomes in the GnomAD database, including 365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.028 (194 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (171 hom.)
• Consequence: PDE7B NM_018945.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.507
• Publications: 3 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 6-136173871-T-C is Benign according to our data. Variant chr6-136173871-T-C is described in ClinVar as Benign. ClinVar VariationId is 792055.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0955 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.786T>C	p.His262His	synonymous	Exon 9 of 13	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.786T>C	p.His262His	synonymous	Exon 9 of 13	ENSP00000310661.6	Q9NP56
	PDE7B	ENST00000615259.4	TSL:1	c.942T>C	p.His314His	synonymous	Exon 8 of 12	ENSP00000482117.1	A1E5M1
	PDE7B-AS1	ENST00000417643.5	TSL:5	n.59-11523A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0283 AC: 4299 AN: 152172 Hom.: 190 Cov.: 32

Gnomad AFR AF: 0.0974

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000720

Gnomad OTH AF: 0.0215

GnomAD2 exomes AF: 0.00755 AC: 1894 AN: 250784 AF XY: 0.00555

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.00598

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000627

Gnomad OTH exome AF: 0.00392

GnomAD4 exome AF: 0.00333 AC: 4859 AN: 1459420 Hom.: 171 Cov.: 29 AF XY: 0.00291 AC XY: 2113 AN XY: 726218

African (AFR) AF: 0.0990 AC: 3302 AN: 33362

American (AMR) AF: 0.00659 AC: 294 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39692

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.0110 AC: 63 AN: 5752

European-Non Finnish (NFE) AF: 0.000647 AC: 718 AN: 1109966

Other (OTH) AF: 0.00759 AC: 458 AN: 60308

GnomAD4 genome AF: 0.0285 AC: 4336 AN: 152290 Hom.: 194 Cov.: 32 AF XY: 0.0278 AC XY: 2069 AN XY: 74492

African (AFR) AF: 0.0980 AC: 4072 AN: 41542

American (AMR) AF: 0.0108 AC: 165 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.000720 AC: 49 AN: 68020

Other (OTH) AF: 0.0213 AC: 45 AN: 2114

Alfa AF: 0.0102 Hom.: 135

Bravo AF: 0.0320

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.000928

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.6
DANN	Benign	0.66
PhyloP100		0.51
Mutation Taster		=99/1	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: rs73555079; hg19: chr6-136495009;