rs215614

Variant names:

• chr7-32307723-G-A
• rs215614
• NM_001322059.2:c.311-98184C>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.311-98184C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,026 control chromosomes in the GnomAD database, including 29,801 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 0.62 (29801 hom., cov: 32)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.892
• Publications: 27 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 (AMR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001322059.2	c.311-98184C>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.311-98184C>T		intron_variant	Intron 1 of 1			ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94399 AN: 151908 Hom.: 29771 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.716

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.622 AC: 94491 AN: 152026 Hom.: 29801 Cov.: 32 AF XY: 0.628 AC XY: 46625 AN XY: 74300

African (AFR) AF: 0.572 AC: 23712 AN: 41420

American (AMR) AF: 0.716 AC: 10946 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3468

East Asian (EAS) AF: 0.395 AC: 2037 AN: 5158

South Asian (SAS) AF: 0.554 AC: 2668 AN: 4820

European-Finnish (FIN) AF: 0.757 AC: 8015 AN: 10582

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43120 AN: 67988

Other (OTH) AF: 0.627 AC: 1320 AN: 2104

Alfa AF: 0.619 Hom.: 84562

Bravo AF: 0.614

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.71
DANN	Benign	0.76
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs215614; hg19: chr7-32347335;