7-31753676-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001191057.4(PDE1C):c.1961-123A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,358,098 control chromosomes in the GnomAD database, including 192 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (104 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (88 hom.)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.334

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 7-31753676-T-G is Benign according to our data. Variant chr7-31753676-T-G is described in ClinVar as [Benign]. Clinvar id is 1229535.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE1C	NM_001191057.4	c.1961-123A>C		intron_variant		ENST00000396191.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE1C	ENST00000396191.6	c.1961-123A>C		intron_variant		2	NM_001191057.4	A1
PDE1C	ENST00000321453.12	c.1961-123A>C		intron_variant		2		A1
PDE1C	ENST00000396193.5	c.2141-123A>C		intron_variant		2		A1

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3128 AN: 152126 Hom.: 100 Cov.: 33

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00518

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00199 AC: 2398 AN: 1205854 Hom.: 88 AF XY: 0.00176 AC XY: 1032 AN XY: 585348

Gnomad4 AFR exome AF: 0.0756

Gnomad4 AMR exome AF: 0.00438

Gnomad4 ASJ exome AF: 0.0000564

Gnomad4 EAS exome AF: 0.0000617

Gnomad4 SAS exome AF: 0.000168

Gnomad4 FIN exome AF: 0.0000241

Gnomad4 NFE exome AF: 0.0000757

Gnomad4 OTH exome AF: 0.00527

GnomAD4 genome AF: 0.0207 AC: 3155 AN: 152244 Hom.: 104 Cov.: 33 AF XY: 0.0204 AC XY: 1519 AN XY: 74434

Gnomad4 AFR AF: 0.0728

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0133

Alfa AF: 0.0156 Hom.: 12

Bravo AF: 0.0236

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 25, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	3.8
Dann	Benign	0.58

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs116123743; hg19: chr7-31793290;