6-135944027-G-A

Position:

• chr6-135944027-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018945.4(PDE7B):​c.22-3437G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,944 control chromosomes in the GnomAD database, including 11,075 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 0.38 (11075 hom., cov: 31)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.22-3437G>A		intron_variant		ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.22-3437G>A		intron_variant		1	NM_018945.4	ENSP00000310661	P1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57358 AN: 151824 Hom.: 11054 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.404

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

GnomAD4 genome AF: 0.378 AC: 57399 AN: 151944 Hom.: 11075 Cov.: 31 AF XY: 0.381 AC XY: 28273 AN XY: 74254

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.401

Alfa AF: 0.383 Hom.: 1959

Bravo AF: 0.396

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.86
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs7774640; hg19: chr6-136265165;