rs2191876

Variant names:

• chr7-31843314-T-C
• rs2191876
• NM_001191057.4:c.980+4654A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-31843314-T-C
• chr7-31843314-T-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.980+4654A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 151,778 control chromosomes in the GnomAD database, including 52,195 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 0.83 (52195 hom., cov: 31)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.942 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.980+4654A>G		intron	N/A	NP_001177986.1
	PDE1C	NM_001191058.4		c.1160+4654A>G		intron	N/A	NP_001177987.2
	PDE1C	NM_001322059.2		c.1385+4654A>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.980+4654A>G		intron	N/A	ENSP00000379494.1
	PDE1C	ENST00000396182.6	TSL:1	c.980+4654A>G		intron	N/A	ENSP00000379485.2
	PDE1C	ENST00000396184.7	TSL:1	c.980+4654A>G		intron	N/A	ENSP00000379487.3

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125605 AN: 151660 Hom.: 52139 Cov.: 31

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.854

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.965

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.748

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.828 AC: 125721 AN: 151778 Hom.: 52195 Cov.: 31 AF XY: 0.832 AC XY: 61669 AN XY: 74150

African (AFR) AF: 0.822 AC: 34110 AN: 41476

American (AMR) AF: 0.854 AC: 12990 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.781 AC: 2703 AN: 3462

East Asian (EAS) AF: 0.965 AC: 4989 AN: 5172

South Asian (SAS) AF: 0.787 AC: 3801 AN: 4830

European-Finnish (FIN) AF: 0.849 AC: 8968 AN: 10564

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.819 AC: 55514 AN: 67750

Other (OTH) AF: 0.813 AC: 1714 AN: 2108

Alfa AF: 0.819 Hom.: 13607

Bravo AF: 0.830

Asia WGS AF: 0.887 AC: 3071 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.40
PhyloP100		-1.0
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: rs2191876; hg19: chr7-31882928;