rs998413

Variant names:

• chr7-31984619-T-C
• rs998413
• NM_001191057.4:c.128+66935A>G

Variant summary

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

The NM_001191057.4(PDE1C):​c.128+66935A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,258 control chromosomes in the GnomAD database, including 907 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 0.10 (907 hom., cov: 32)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.778
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191057.4	c.128+66935A>G		intron_variant	Intron 2 of 17	ENST00000396191.6	NP_001177986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000396191.6	c.128+66935A>G		intron_variant	Intron 2 of 17	2	NM_001191057.4	ENSP00000379494.1

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15752 AN: 152140 Hom.: 907 Cov.: 32

Gnomad AFR AF: 0.0864

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.0137

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.104 AC: 15763 AN: 152258 Hom.: 907 Cov.: 32 AF XY: 0.102 AC XY: 7623 AN XY: 74460

African (AFR) AF: 0.0866 AC: 3596 AN: 41546

American (AMR) AF: 0.102 AC: 1556 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 526 AN: 3468

East Asian (EAS) AF: 0.0137 AC: 71 AN: 5180

South Asian (SAS) AF: 0.136 AC: 654 AN: 4820

European-Finnish (FIN) AF: 0.0742 AC: 788 AN: 10614

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8235 AN: 68014

Other (OTH) AF: 0.105 AC: 222 AN: 2110

Alfa AF: 0.119 Hom.: 1941

Bravo AF: 0.102

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.60
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs998413; hg19: chr7-32024231;