7-31815955-G-A

Variant names:

• chr7-31815955-G-A
• rs2302450
• NM_001191057.4:c.1782C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001191057.4(PDE1C):​c.1782C>T​(p.Ala594Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 1,612,540 control chromosomes in the GnomAD database, including 46,070 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4217 hom., cov: 32)
  • Exomes 𝑓: 0.23 (41853 hom.)
• Consequence: PDE1C NM_001191057.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.35
• Publications: 19 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-31815955-G-A is Benign according to our data. Variant chr7-31815955-G-A is described in ClinVar as Benign. ClinVar VariationId is 1234874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.272 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	NM_001191057.4	MANE Select	c.1782C>T	p.Ala594Ala	synonymous	Exon 15 of 18	NP_001177986.1	Q14123-1
	PDE1C	NM_001191058.4		c.1962C>T	p.Ala654Ala	synonymous	Exon 16 of 19	NP_001177987.2	A0A0A0MS69
	PDE1C	NM_001322059.2		c.2187C>T	p.Ala729Ala	synonymous	Exon 16 of 18	NP_001308988.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	ENST00000396191.6	TSL:2 MANE Select	c.1782C>T	p.Ala594Ala	synonymous	Exon 15 of 18	ENSP00000379494.1	Q14123-1
	PDE1C	ENST00000396182.6	TSL:1	c.1782C>T	p.Ala594Ala	synonymous	Exon 15 of 17	ENSP00000379485.2	Q14123-2
	PDE1C	ENST00000396184.7	TSL:1	c.1782C>T	p.Ala594Ala	synonymous	Exon 16 of 18	ENSP00000379487.3	Q14123-2

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35325 AN: 151916 Hom.: 4219 Cov.: 32

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.231 AC: 58170 AN: 251362 AF XY: 0.240

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.354

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.170

Gnomad NFE exome AF: 0.249

Gnomad OTH exome AF: 0.252

GnomAD4 exome AF: 0.235 AC: 342782 AN: 1460506 Hom.: 41853 Cov.: 31 AF XY: 0.238 AC XY: 173168 AN XY: 726626

African (AFR) AF: 0.229 AC: 7657 AN: 33450

American (AMR) AF: 0.150 AC: 6713 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9327 AN: 26112

East Asian (EAS) AF: 0.178 AC: 7076 AN: 39688

South Asian (SAS) AF: 0.297 AC: 25618 AN: 86220

European-Finnish (FIN) AF: 0.170 AC: 9077 AN: 53420

Middle Eastern (MID) AF: 0.344 AC: 1985 AN: 5762

European-Non Finnish (NFE) AF: 0.234 AC: 260476 AN: 1110810

Other (OTH) AF: 0.246 AC: 14853 AN: 60336

GnomAD4 genome AF: 0.232 AC: 35335 AN: 152034 Hom.: 4217 Cov.: 32 AF XY: 0.227 AC XY: 16873 AN XY: 74314

African (AFR) AF: 0.227 AC: 9412 AN: 41486

American (AMR) AF: 0.210 AC: 3205 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3468

East Asian (EAS) AF: 0.168 AC: 864 AN: 5152

South Asian (SAS) AF: 0.284 AC: 1370 AN: 4816

European-Finnish (FIN) AF: 0.174 AC: 1840 AN: 10594

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16517 AN: 67946

Other (OTH) AF: 0.264 AC: 558 AN: 2110

Alfa AF: 0.247 Hom.: 12411

Bravo AF: 0.234

Asia WGS AF: 0.208 AC: 725 AN: 3476

EpiCase AF: 0.266

EpiControl AF: 0.270

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hearing loss, autosomal dominant 74 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.31
DANN	Benign	0.80
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: rs2302450; hg19: chr7-31855569; COSMIC: COSV58507186;