7-32188366-C-G

Variant names:

• chr7-32188366-C-G
• rs10263213
• NM_001191058.4:c.137-18410G>C

Variant summary

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

The NM_001191058.4(PDE1C):​c.137-18410G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,824 control chromosomes in the GnomAD database, including 9,666 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 0.34 (9666 hom., cov: 32)
• Consequence: PDE1C NM_001191058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 1 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)

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 = 0.489 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	NM_001191058.4		c.137-18410G>C		intron	N/A	NP_001177987.2
	PDE1C	NM_001322059.2		c.362-18410G>C		intron	N/A	NP_001308988.1
	PDE1C	NM_001322058.2		c.137-18410G>C		intron	N/A	NP_001308987.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	ENST00000396193.5	TSL:2	c.137-18410G>C		intron	N/A	ENSP00000379496.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51800 AN: 151706 Hom.: 9651 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.342 AC: 51860 AN: 151824 Hom.: 9666 Cov.: 32 AF XY: 0.342 AC XY: 25368 AN XY: 74222

African (AFR) AF: 0.489 AC: 20248 AN: 41410

American (AMR) AF: 0.303 AC: 4618 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3466

East Asian (EAS) AF: 0.505 AC: 2612 AN: 5170

South Asian (SAS) AF: 0.291 AC: 1403 AN: 4822

European-Finnish (FIN) AF: 0.272 AC: 2863 AN: 10536

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18351 AN: 67858

Other (OTH) AF: 0.322 AC: 680 AN: 2110

Alfa AF: 0.172 Hom.: 357

Bravo AF: 0.356

Asia WGS AF: 0.352 AC: 1227 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.37
PhyloP100		0.32
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: rs10263213; hg19: chr7-32227978;