6-136187261-T-C

Variant names:

• chr6-136187261-T-C
• rs3734548
• NM_018945.4:c.1126+145T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018945.4(PDE7B):​c.1126+145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 589,298 control chromosomes in the GnomAD database, including 16,084 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 0.24 (11807 hom., cov: 32)
  • Exomes 𝑓: 0.064 (4277 hom.)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4	c.1126+145T>C		intron_variant	Intron 12 of 12	ENST00000308191.11	NP_061818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11	c.1126+145T>C		intron_variant	Intron 12 of 12	1	NM_018945.4	ENSP00000310661.6

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35763 AN: 152106 Hom.: 11750 Cov.: 32

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0254

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.0643 AC: 28118 AN: 437076 Hom.: 4277 AF XY: 0.0632 AC XY: 14674 AN XY: 232030

African (AFR) AF: 0.731 AC: 8221 AN: 11250

American (AMR) AF: 0.0708 AC: 980 AN: 13840

Ashkenazi Jewish (ASJ) AF: 0.0301 AC: 411 AN: 13664

East Asian (EAS) AF: 0.195 AC: 5775 AN: 29614

South Asian (SAS) AF: 0.105 AC: 3915 AN: 37178

European-Finnish (FIN) AF: 0.0355 AC: 1233 AN: 34730

Middle Eastern (MID) AF: 0.0641 AC: 178 AN: 2778

European-Non Finnish (NFE) AF: 0.0190 AC: 5105 AN: 268430

Other (OTH) AF: 0.0899 AC: 2300 AN: 25592

GnomAD4 genome AF: 0.236 AC: 35887 AN: 152222 Hom.: 11807 Cov.: 32 AF XY: 0.231 AC XY: 17168 AN XY: 74426

African (AFR) AF: 0.739 AC: 30676 AN: 41494

American (AMR) AF: 0.104 AC: 1596 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0254 AC: 88 AN: 3470

East Asian (EAS) AF: 0.166 AC: 862 AN: 5186

South Asian (SAS) AF: 0.116 AC: 560 AN: 4830

European-Finnish (FIN) AF: 0.0377 AC: 400 AN: 10618

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0183 AC: 1247 AN: 68008

Other (OTH) AF: 0.203 AC: 429 AN: 2110

Alfa AF: 0.134 Hom.: 1818

Bravo AF: 0.264

Asia WGS AF: 0.214 AC: 742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.8
DANN	Benign	0.60
PhyloP100		-0.32
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: rs3734548; hg19: chr6-136508399;