7-31809092-A-G

Variant names:

• chr7-31809092-A-G
• rs3213709
• NM_001191057.4:c.1830T>C

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.1830T>C​(p.Gly610Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,582,904 control chromosomes in the GnomAD database, including 30,873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3092 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27781 hom.)
• Consequence: PDE1C NM_001191057.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0620
• Publications: 18 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=-0.51).
• BP6: Variant 7-31809092-A-G is Benign according to our data. Variant chr7-31809092-A-G is described in ClinVar as Benign. ClinVar VariationId is 1241492.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.062 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.213 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.1830T>C	p.Gly610Gly	synonymous	Exon 16 of 18	NP_001177986.1	Q14123-1
	PDE1C	NM_001191058.4		c.2010T>C	p.Gly670Gly	synonymous	Exon 17 of 19	NP_001177987.2	A0A0A0MS69
	PDE1C	NM_001322059.2		c.2235T>C	p.Gly745Gly	synonymous	Exon 17 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.1830T>C	p.Gly610Gly	synonymous	Exon 16 of 18	ENSP00000379494.1	Q14123-1
	PDE1C	ENST00000396182.6	TSL:1	c.1830T>C	p.Gly610Gly	synonymous	Exon 16 of 17	ENSP00000379485.2	Q14123-2
	PDE1C	ENST00000396184.7	TSL:1	c.1830T>C	p.Gly610Gly	synonymous	Exon 17 of 18	ENSP00000379487.3	Q14123-2

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30170 AN: 151776 Hom.: 3093 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.215

GnomAD2 exomes AF: 0.193 AC: 48076 AN: 248792 AF XY: 0.199

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.306

Gnomad EAS exome AF: 0.136

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.193 AC: 275697 AN: 1431010 Hom.: 27781 Cov.: 26 AF XY: 0.195 AC XY: 139424 AN XY: 713878

African (AFR) AF: 0.212 AC: 6945 AN: 32788

American (AMR) AF: 0.148 AC: 6590 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 7901 AN: 25746

East Asian (EAS) AF: 0.144 AC: 5652 AN: 39288

South Asian (SAS) AF: 0.239 AC: 20387 AN: 85386

European-Finnish (FIN) AF: 0.142 AC: 7544 AN: 53028

Middle Eastern (MID) AF: 0.274 AC: 1554 AN: 5676

European-Non Finnish (NFE) AF: 0.191 AC: 206810 AN: 1085374

Other (OTH) AF: 0.208 AC: 12314 AN: 59244

GnomAD4 genome AF: 0.199 AC: 30194 AN: 151894 Hom.: 3092 Cov.: 32 AF XY: 0.195 AC XY: 14468 AN XY: 74240

African (AFR) AF: 0.211 AC: 8751 AN: 41456

American (AMR) AF: 0.192 AC: 2915 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1095 AN: 3472

East Asian (EAS) AF: 0.135 AC: 695 AN: 5136

South Asian (SAS) AF: 0.224 AC: 1080 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1469 AN: 10590

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13552 AN: 67888

Other (OTH) AF: 0.212 AC: 449 AN: 2114

Alfa AF: 0.208 Hom.: 7558

Bravo AF: 0.204

Asia WGS AF: 0.157 AC: 545 AN: 3474

EpiCase AF: 0.215

EpiControl AF: 0.221

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	-0.51
CADD	Benign	6.2
DANN	Benign	0.76
PhyloP100		0.062
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
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: rs3213709; hg19: chr7-31848706; COSMIC: COSV58507169;