rs4723127

Variant names:

• chr7-32185671-T-G
• rs4723127
• NM_001191058.4:c.137-15715A>C

Variant summary

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

The NM_001191058.4(PDE1C):​c.137-15715A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 152,098 control chromosomes in the GnomAD database, including 11,262 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 0.37 (11262 hom., cov: 33)
• Consequence: PDE1C NM_001191058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 3 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.426 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191058.4	c.137-15715A>C		intron_variant	Intron 2 of 18		NP_001177987.2
PDE1C	NM_001322059.2	c.362-15715A>C		intron_variant	Intron 2 of 17		NP_001308988.1
PDE1C	NM_001322058.2	c.137-15715A>C		intron_variant	Intron 2 of 17		NP_001308987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000396193.5	c.137-15715A>C		intron_variant	Intron 2 of 18	2		ENSP00000379496.1

Frequencies

GnomAD3 genomes AF: 0.369 AC: 56128 AN: 151980 Hom.: 11254 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.369 AC: 56152 AN: 152098 Hom.: 11262 Cov.: 33 AF XY: 0.375 AC XY: 27874 AN XY: 74368

African (AFR) AF: 0.214 AC: 8878 AN: 41512

American (AMR) AF: 0.430 AC: 6575 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1411 AN: 3472

East Asian (EAS) AF: 0.265 AC: 1375 AN: 5186

South Asian (SAS) AF: 0.424 AC: 2040 AN: 4816

European-Finnish (FIN) AF: 0.511 AC: 5386 AN: 10544

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29220 AN: 67974

Other (OTH) AF: 0.369 AC: 779 AN: 2110

Alfa AF: 0.410 Hom.: 10117

Bravo AF: 0.353

Asia WGS AF: 0.364 AC: 1261 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.61
PhyloP100		-1.2
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: rs4723127; hg19: chr7-32225283;