7-32382465-G-C

Variant names:

• chr7-32382465-G-C
• rs441261
• NM_001322059.2:c.310+45357C>G

Variant summary

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

The NM_001322059.2(PDE1C):​c.310+45357C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 152,076 control chromosomes in the GnomAD database, including 44,851 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 0.75 (44851 hom., cov: 31)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001322059.2	c.310+45357C>G		intron_variant	Intron 1 of 17		NP_001308988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000672256.1	c.310+45357C>G		intron_variant	Intron 1 of 1			ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114171 AN: 151958 Hom.: 44851 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.749

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.751 AC: 114192 AN: 152076 Hom.: 44851 Cov.: 31 AF XY: 0.750 AC XY: 55770 AN XY: 74346

African (AFR) AF: 0.501 AC: 20782 AN: 41460

American (AMR) AF: 0.862 AC: 13172 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.749 AC: 2598 AN: 3470

East Asian (EAS) AF: 0.963 AC: 4959 AN: 5152

South Asian (SAS) AF: 0.692 AC: 3328 AN: 4810

European-Finnish (FIN) AF: 0.825 AC: 8727 AN: 10582

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.852 AC: 57942 AN: 68002

Other (OTH) AF: 0.772 AC: 1629 AN: 2110

Alfa AF: 0.743 Hom.: 2506

Bravo AF: 0.747

Asia WGS AF: 0.794 AC: 2761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.38
PhyloP100		-0.073

Splicing

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

Other links and lift over

dbSNP: rs441261; hg19: chr7-32422077;