rs3734548

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-136187261-T-A
• chr6-136187261-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018945.4(PDE7B):​c.1126+145T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 437,206 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: PDE7B NM_018945.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000229 AC: 1 AN: 437206 Hom.: 0 AF XY: 0.00000431 AC XY: 1 AN XY: 232086

African (AFR) AF: 0.00 AC: 0 AN: 11272

American (AMR) AF: 0.00 AC: 0 AN: 13844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13666

East Asian (EAS) AF: 0.00 AC: 0 AN: 29642

South Asian (SAS) AF: 0.00 AC: 0 AN: 37206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2782

European-Non Finnish (NFE) AF: 0.00000373 AC: 1 AN: 268454

Other (OTH) AF: 0.00 AC: 0 AN: 25602

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.7
DANN	Benign	0.66
PhyloP100		-0.32

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;