NM_001191058.4:c.308+19857T>G

Variant names:

• chr7-32149928-A-C
• rs11975235
• NM_001191058.4:c.308+19857T>G

Variant summary

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

The NM_001191058.4(PDE1C):​c.308+19857T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,028 control chromosomes in the GnomAD database, including 13,585 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 0.42 (13585 hom., cov: 32)
• Consequence: PDE1C NM_001191058.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 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.308+19857T>G		intron	N/A	NP_001177987.2
	PDE1C	NM_001322059.2		c.533+19857T>G		intron	N/A	NP_001308988.1
	PDE1C	NM_001322058.2		c.308+19857T>G		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.308+19857T>G		intron	N/A	ENSP00000379496.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63311 AN: 151910 Hom.: 13583 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.444

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

GnomAD4 genome AF: 0.417 AC: 63333 AN: 152028 Hom.: 13585 Cov.: 32 AF XY: 0.419 AC XY: 31110 AN XY: 74326

African (AFR) AF: 0.333 AC: 13818 AN: 41464

American (AMR) AF: 0.433 AC: 6620 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1988 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2865 AN: 5152

South Asian (SAS) AF: 0.421 AC: 2029 AN: 4824

European-Finnish (FIN) AF: 0.465 AC: 4907 AN: 10558

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.435 AC: 29558 AN: 67974

Other (OTH) AF: 0.442 AC: 930 AN: 2106

Alfa AF: 0.406 Hom.: 9872

Bravo AF: 0.414

Asia WGS AF: 0.419 AC: 1461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.0
DANN	Benign	0.68
PhyloP100		0.55
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: rs11975235; hg19: chr7-32189540;