7-31815964-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001191057.4(PDE1C):c.1773C>T(p.Asn591=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.977 in 1,613,948 control chromosomes in the GnomAD database, including 770,436 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.97 (71502 hom., cov: 32)
  • Exomes 𝑓: 0.98 (698934 hom.)
• Consequence: PDE1C NM_001191057.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.118

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-31815964-G-A is Benign according to our data. Variant chr7-31815964-G-A is described in ClinVar as [Benign]. Clinvar id is 1233118.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.118 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4	c.1773C>T	p.Asn591=	synonymous_variant	15/18	ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6	c.1773C>T	p.Asn591=	synonymous_variant	15/18	2	NM_001191057.4	A1

Frequencies

GnomAD3 genomes AF: 0.969 AC: 147420 AN: 152140 Hom.: 71449 Cov.: 32

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.976

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.932

Gnomad SAS AF: 0.960

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.980

Gnomad OTH AF: 0.963

GnomAD3 exomes AF: 0.972 AC: 244324 AN: 251418 Hom.: 118795 AF XY: 0.972 AC XY: 132120 AN XY: 135890

Gnomad AFR exome AF: 0.943

Gnomad AMR exome AF: 0.987

Gnomad ASJ exome AF: 0.966

Gnomad EAS exome AF: 0.930

Gnomad SAS exome AF: 0.959

Gnomad FIN exome AF: 0.993

Gnomad NFE exome AF: 0.978

Gnomad OTH exome AF: 0.973

GnomAD4 exome AF: 0.978 AC: 1429267 AN: 1461690 Hom.: 698934 Cov.: 53 AF XY: 0.977 AC XY: 710668 AN XY: 727166

Gnomad4 AFR exome AF: 0.941

Gnomad4 AMR exome AF: 0.987

Gnomad4 ASJ exome AF: 0.966

Gnomad4 EAS exome AF: 0.925

Gnomad4 SAS exome AF: 0.961

Gnomad4 FIN exome AF: 0.993

Gnomad4 NFE exome AF: 0.982

Gnomad4 OTH exome AF: 0.973

GnomAD4 genome AF: 0.969 AC: 147532 AN: 152258 Hom.: 71502 Cov.: 32 AF XY: 0.969 AC XY: 72155 AN XY: 74428

Gnomad4 AFR AF: 0.946

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 0.969

Gnomad4 EAS AF: 0.932

Gnomad4 SAS AF: 0.960

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.980

Gnomad4 OTH AF: 0.963

Alfa AF: 0.977 Hom.: 115528

Bravo AF: 0.967

Asia WGS AF: 0.940 AC: 3266 AN: 3476

EpiCase AF: 0.978

EpiControl AF: 0.976

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Hearing loss, autosomal dominant 74 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.33
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1860790; hg19: chr7-31855578;