7-32329353-G-A

Variant names:

• chr7-32329353-G-A
• rs6462356
• NM_001322059.2:c.310+98469C>T

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+98469C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 152,258 control chromosomes in the GnomAD database, including 131 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 0.030 (131 hom., cov: 32)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001322059.2	c.310+98469C>T		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+98469C>T		intron_variant	Intron 1 of 1			ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.0303 AC: 4610 AN: 152140 Hom.: 131 Cov.: 32

Gnomad AFR AF: 0.0743

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00953

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0320

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

GnomAD4 genome AF: 0.0303 AC: 4614 AN: 152258 Hom.: 131 Cov.: 32 AF XY: 0.0285 AC XY: 2118 AN XY: 74442

African (AFR) AF: 0.0742 AC: 3080 AN: 41530

American (AMR) AF: 0.0156 AC: 238 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4824

European-Finnish (FIN) AF: 0.0114 AC: 121 AN: 10610

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 894 AN: 68026

Other (OTH) AF: 0.0317 AC: 67 AN: 2114

Alfa AF: 0.0164 Hom.: 60

Bravo AF: 0.0327

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.023
DANN	Benign	0.58
PhyloP100		-2.1

Splicing

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

Other links and lift over

dbSNP: rs6462356; hg19: chr7-32368965;