NM_001191057.4:c.129-53501A>G

Variant names:

• chr7-31934361-T-C
• rs11770536
• NM_001191057.4:c.129-53501A>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.129-53501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,020 control chromosomes in the GnomAD database, including 22,980 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 0.55 (22980 hom., cov: 32)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.589
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191057.4. 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_001191057.4	MANE Select	c.129-53501A>G		intron	N/A	NP_001177986.1
	PDE1C	NM_001191058.4		c.309-53501A>G		intron	N/A	NP_001177987.2
	PDE1C	NM_001322059.2		c.534-53501A>G		intron	N/A	NP_001308988.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	ENST00000396191.6	TSL:2 MANE Select	c.129-53501A>G		intron	N/A	ENSP00000379494.1
	PDE1C	ENST00000396182.6	TSL:1	c.129-53501A>G		intron	N/A	ENSP00000379485.2
	PDE1C	ENST00000396184.7	TSL:1	c.129-53501A>G		intron	N/A	ENSP00000379487.3

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83152 AN: 151902 Hom.: 22976 Cov.: 32

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.606

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.628

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.547 AC: 83198 AN: 152020 Hom.: 22980 Cov.: 32 AF XY: 0.546 AC XY: 40557 AN XY: 74284

African (AFR) AF: 0.545 AC: 22595 AN: 41470

American (AMR) AF: 0.498 AC: 7595 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1564 AN: 3472

East Asian (EAS) AF: 0.456 AC: 2361 AN: 5172

South Asian (SAS) AF: 0.376 AC: 1811 AN: 4814

European-Finnish (FIN) AF: 0.628 AC: 6626 AN: 10558

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.572 AC: 38881 AN: 67954

Other (OTH) AF: 0.511 AC: 1078 AN: 2110

Alfa AF: 0.546 Hom.: 21968

Bravo AF: 0.540

Asia WGS AF: 0.432 AC: 1503 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.44
PhyloP100		-0.59
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: rs11770536; hg19: chr7-31973974;