rs215605

Variant names:

• chr7-32297353-G-T
• rs215605
• NM_001191058.4:c.85+1298C>A

Variant summary

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

The NM_001191058.4(PDE1C):​c.85+1298C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 151,806 control chromosomes in the GnomAD database, including 24,216 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 0.54 (24216 hom., cov: 30)
• Consequence: PDE1C NM_001191058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 15 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.679 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.85+1298C>A		intron	N/A	NP_001177987.2
	PDE1C	NM_001322059.2		c.311-87814C>A		intron	N/A	NP_001308988.1
	PDE1C	NM_001322058.2		c.85+1298C>A		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.85+1298C>A		intron	N/A	ENSP00000379496.1
	PDE1C	ENST00000672256.1		c.311-87814C>A		intron	N/A	ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.537 AC: 81521 AN: 151686 Hom.: 24216 Cov.: 30

Gnomad AFR AF: 0.284

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.689

Gnomad ASJ AF: 0.541

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.537 AC: 81553 AN: 151806 Hom.: 24216 Cov.: 30 AF XY: 0.546 AC XY: 40516 AN XY: 74200

African (AFR) AF: 0.283 AC: 11721 AN: 41362

American (AMR) AF: 0.690 AC: 10525 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 1879 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1908 AN: 5132

South Asian (SAS) AF: 0.544 AC: 2606 AN: 4794

European-Finnish (FIN) AF: 0.761 AC: 8042 AN: 10566

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42846 AN: 67910

Other (OTH) AF: 0.568 AC: 1201 AN: 2114

Alfa AF: 0.602 Hom.: 47682

Bravo AF: 0.517

Asia WGS AF: 0.497 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.4
DANN	Benign	0.55
PhyloP100		0.26
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: rs215605; hg19: chr7-32336965;