6-135884533-G-A

Variant names:

• chr6-135884533-G-A
• rs9321540
• NM_018945.4:c.21+32514G>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.21+32514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 151,952 control chromosomes in the GnomAD database, including 203 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 0.037 (203 hom., cov: 32)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273
• Publications: 1 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]

ENSG00000288054 (HGNC:):

AHI1-DT (HGNC:32526): (AHI1 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE7B	NM_018945.4	MANE Select	c.21+32514G>A		intron	N/A	NP_061818.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE7B	ENST00000308191.11	TSL:1 MANE Select	c.21+32514G>A		intron	N/A	ENSP00000310661.6
	ENSG00000288054	ENST00000668291.1		n.2351-187C>T		intron	N/A
	AHI1-DT	ENST00000808297.1		n.503-9962G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 5571 AN: 151834 Hom.: 201 Cov.: 32

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0723

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0387

Gnomad FIN AF: 0.0334

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0365

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

GnomAD4 genome AF: 0.0368 AC: 5585 AN: 151952 Hom.: 203 Cov.: 32 AF XY: 0.0393 AC XY: 2920 AN XY: 74260

African (AFR) AF: 0.0591 AC: 2449 AN: 41440

American (AMR) AF: 0.0725 AC: 1106 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 117 AN: 3466

East Asian (EAS) AF: 0.114 AC: 591 AN: 5170

South Asian (SAS) AF: 0.0390 AC: 187 AN: 4796

European-Finnish (FIN) AF: 0.0334 AC: 352 AN: 10550

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0101 AC: 685 AN: 67964

Other (OTH) AF: 0.0394 AC: 83 AN: 2106

Alfa AF: 0.0234 Hom.: 32

Bravo AF: 0.0417

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.80
DANN	Benign	0.69
PhyloP100		-0.27
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: rs9321540; hg19: chr6-136205671;