7-31864413-C-T

Variant names:

• chr7-31864413-C-T
• rs2270221
• NM_001191057.4:c.750+529G>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.750+529G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 151,852 control chromosomes in the GnomAD database, including 6,965 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 0.30 (6965 hom., cov: 33)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 13 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 = 0.36 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.750+529G>A		intron	N/A	NP_001177986.1
	PDE1C	NM_001191058.4		c.930+529G>A		intron	N/A	NP_001177987.2
	PDE1C	NM_001322059.2		c.1155+529G>A		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.750+529G>A		intron	N/A	ENSP00000379494.1
	PDE1C	ENST00000396182.6	TSL:1	c.750+529G>A		intron	N/A	ENSP00000379485.2
	PDE1C	ENST00000396184.7	TSL:1	c.750+529G>A		intron	N/A	ENSP00000379487.3

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45343 AN: 151732 Hom.: 6956 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.299 AC: 45391 AN: 151852 Hom.: 6965 Cov.: 33 AF XY: 0.299 AC XY: 22199 AN XY: 74216

African (AFR) AF: 0.326 AC: 13488 AN: 41414

American (AMR) AF: 0.365 AC: 5570 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1214 AN: 3466

East Asian (EAS) AF: 0.294 AC: 1512 AN: 5150

South Asian (SAS) AF: 0.375 AC: 1800 AN: 4806

European-Finnish (FIN) AF: 0.249 AC: 2623 AN: 10530

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18165 AN: 67932

Other (OTH) AF: 0.329 AC: 693 AN: 2108

Alfa AF: 0.286 Hom.: 21012

Bravo AF: 0.308

Asia WGS AF: 0.314 AC: 1089 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.041
DANN	Benign	0.63
PhyloP100		-2.3
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: rs2270221; hg19: chr7-31904027;