rs12534148

Variant names:

• chr7-32208699-G-A
• rs12534148
• NM_001191058.4:c.136+790C>T

Variant summary

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

The NM_001191058.4(PDE1C):​c.136+790C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,842 control chromosomes in the GnomAD database, including 3,314 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 0.20 (3314 hom., cov: 31)
• Consequence: PDE1C NM_001191058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 2 publications found

Genes affected

PDE1C (HGNC:8776): (phosphodiesterase 1C) This gene encodes an enzyme that belongs to the 3'5'-cyclic nucleotide phosphodiesterase family. Members of this family catalyze hydrolysis of the cyclic nucleotides, cyclic adenosine monophosphate and cyclic guanosine monophosphate, to the corresponding nucleoside 5'-monophosphates. The enzyme encoded by this gene regulates proliferation and migration of vascular smooth muscle cells, and neointimal hyperplasia. This enzyme also plays a role in pathological vascular remodeling by regulating the stability of growth factor receptors, such as PDGF-receptor-beta. [provided by RefSeq, Jul 2016]

PDE1C Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 74

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000300776 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.247 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191058.4. 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
	PDE1C	NM_001191058.4		c.136+790C>T		intron	N/A	NP_001177987.2	A0A0A0MS69
	PDE1C	NM_001322059.2		c.361+790C>T		intron	N/A	NP_001308988.1
	PDE1C	NM_001322058.2		c.136+790C>T		intron	N/A	NP_001308987.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	ENST00000396193.5	TSL:2	c.136+790C>T		intron	N/A	ENSP00000379496.1	A0A0A0MS69
	ENSG00000300776	ENST00000773962.1		n.342+2742G>A		intron	N/A
	ENSG00000300776	ENST00000773963.1		n.341-1698G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29960 AN: 151728 Hom.: 3313 Cov.: 31

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.197 AC: 29966 AN: 151842 Hom.: 3314 Cov.: 31 AF XY: 0.195 AC XY: 14463 AN XY: 74222

African (AFR) AF: 0.109 AC: 4531 AN: 41390

American (AMR) AF: 0.193 AC: 2947 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1062 AN: 5154

South Asian (SAS) AF: 0.200 AC: 960 AN: 4806

European-Finnish (FIN) AF: 0.203 AC: 2143 AN: 10532

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.250 AC: 16998 AN: 67930

Other (OTH) AF: 0.195 AC: 411 AN: 2112

Alfa AF: 0.232 Hom.: 7018

Bravo AF: 0.195

Asia WGS AF: 0.176 AC: 608 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	0.085
DANN	Benign	0.74
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12534148; hg19: chr7-32248311;