rs215702

Variant names:

• chr7-32360046-G-A
• rs215702
• NM_001322059.2:c.310+67776C>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+67776C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 151,940 control chromosomes in the GnomAD database, including 25,632 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 0.56 (25632 hom., cov: 31)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 7 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 (AMR) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001322059.2	c.310+67776C>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+67776C>T		intron_variant	Intron 1 of 1			ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85684 AN: 151822 Hom.: 25616 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.564 AC: 85743 AN: 151940 Hom.: 25632 Cov.: 31 AF XY: 0.564 AC XY: 41903 AN XY: 74264

African (AFR) AF: 0.385 AC: 15961 AN: 41424

American (AMR) AF: 0.687 AC: 10489 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1714 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1902 AN: 5154

South Asian (SAS) AF: 0.393 AC: 1884 AN: 4796

European-Finnish (FIN) AF: 0.708 AC: 7467 AN: 10546

Middle Eastern (MID) AF: 0.514 AC: 150 AN: 292

European-Non Finnish (NFE) AF: 0.653 AC: 44363 AN: 67962

Other (OTH) AF: 0.564 AC: 1191 AN: 2112

Alfa AF: 0.610 Hom.: 16291

Bravo AF: 0.557

Asia WGS AF: 0.424 AC: 1478 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	0.71
DANN	Benign	0.47
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs215702; hg19: chr7-32399658;