rs7774640

Variant names:

• chr6-135944027-G-A
• rs7774640
• NM_018945.4:c.22-3437G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.22-3437G>A		intron	N/A	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.22-3437G>A		intron	N/A	ENSP00000310661.6	Q9NP56

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

African (AFR) AF: 0.346 AC: 14342 AN: 41436

American (AMR) AF: 0.516 AC: 7879 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1281 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2352 AN: 5156

South Asian (SAS) AF: 0.335 AC: 1610 AN: 4802

European-Finnish (FIN) AF: 0.359 AC: 3795 AN: 10562

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24817 AN: 67944

Other (OTH) AF: 0.401 AC: 844 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.86
DANN	Benign	0.68
PhyloP100		-0.29
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: rs7774640; hg19: chr6-136265165;