7-32403507-T-C

Variant names:

• chr7-32403507-T-C
• rs215736
• NM_001322059.2:c.310+24315A>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+24315A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 152,164 control chromosomes in the GnomAD database, including 59,519 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 0.87 (59519 hom., cov: 32)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322059.2. 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_001322059.2		c.310+24315A>G		intron	N/A	NP_001308988.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	ENST00000672256.1		c.310+24315A>G		intron	N/A	ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.875 AC: 133044 AN: 152046 Hom.: 59517 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.918

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.873

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

GnomAD4 genome AF: 0.875 AC: 133089 AN: 152164 Hom.: 59519 Cov.: 32 AF XY: 0.875 AC XY: 65111 AN XY: 74380

African (AFR) AF: 0.667 AC: 27620 AN: 41418

American (AMR) AF: 0.914 AC: 13988 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 3185 AN: 3468

East Asian (EAS) AF: 0.992 AC: 5119 AN: 5162

South Asian (SAS) AF: 0.824 AC: 3979 AN: 4828

European-Finnish (FIN) AF: 0.974 AC: 10350 AN: 10624

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.968 AC: 65840 AN: 68038

Other (OTH) AF: 0.874 AC: 1849 AN: 2116

Alfa AF: 0.924 Hom.: 28310

Bravo AF: 0.862

Asia WGS AF: 0.884 AC: 3073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.8
DANN	Benign	0.30
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs215736; hg19: chr7-32443119;