rs917749

Variant names:

• chr7-31755541-C-T
• rs917749
• NM_001191057.4:c.1961-1988G>A

Variant summary

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

The NM_001191057.4(PDE1C):​c.1961-1988G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 151,288 control chromosomes in the GnomAD database, including 36,258 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 0.69 (36258 hom., cov: 30)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0870
• Publications: 2 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191057.4	c.1961-1988G>A		intron_variant	Intron 17 of 17	ENST00000396191.6	NP_001177986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000396191.6	c.1961-1988G>A		intron_variant	Intron 17 of 17	2	NM_001191057.4	ENSP00000379494.1
PDE1C	ENST00000396193.5	c.2141-1988G>A		intron_variant	Intron 18 of 18	2		ENSP00000379496.1
PDE1C	ENST00000321453.12	c.1961-1988G>A		intron_variant	Intron 18 of 18	2		ENSP00000318105.7

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104201 AN: 151168 Hom.: 36241 Cov.: 30

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.789

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.689 AC: 104253 AN: 151288 Hom.: 36258 Cov.: 30 AF XY: 0.682 AC XY: 50391 AN XY: 73886

African (AFR) AF: 0.697 AC: 28714 AN: 41200

American (AMR) AF: 0.617 AC: 9365 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 2731 AN: 3460

East Asian (EAS) AF: 0.454 AC: 2325 AN: 5124

South Asian (SAS) AF: 0.732 AC: 3524 AN: 4814

European-Finnish (FIN) AF: 0.648 AC: 6747 AN: 10420

Middle Eastern (MID) AF: 0.806 AC: 232 AN: 288

European-Non Finnish (NFE) AF: 0.717 AC: 48597 AN: 67794

Other (OTH) AF: 0.720 AC: 1511 AN: 2100

Alfa AF: 0.708 Hom.: 114342

Bravo AF: 0.686

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.087
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: rs917749; hg19: chr7-31795155;