chr7-31809149-T-C

Variant names:

• chr7-31809149-T-C
• rs113385926
• NM_001191057.4:c.1814-41A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001191057.4(PDE1C):​c.1814-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 1,086,620 control chromosomes in the GnomAD database, including 1,379 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.047 (192 hom., cov: 32)
  • Exomes 𝑓: 0.048 (1187 hom.)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.679

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 2 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-31809149-T-C is Benign according to our data. Variant chr7-31809149-T-C is described in ClinVar as [Benign]. Clinvar id is 1273421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191057.4	c.1814-41A>G		intron_variant	Intron 15 of 17	ENST00000396191.6	NP_001177986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000396191.6	c.1814-41A>G		intron_variant	Intron 15 of 17	2	NM_001191057.4	ENSP00000379494.1

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 7151 AN: 151992 Hom.: 192 Cov.: 32

Gnomad AFR AF: 0.0462

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0472

Gnomad OTH AF: 0.0439

GnomAD2 exomes AF: 0.0489 AC: 11597 AN: 237154 AF XY: 0.0508

Gnomad AFR exome AF: 0.0483

Gnomad AMR exome AF: 0.0188

Gnomad ASJ exome AF: 0.0247

Gnomad EAS exome AF: 0.0454

Gnomad FIN exome AF: 0.0775

Gnomad NFE exome AF: 0.0485

Gnomad OTH exome AF: 0.0450

GnomAD4 exome AF: 0.0477 AC: 44621 AN: 934506 Hom.: 1187 Cov.: 13 AF XY: 0.0487 AC XY: 23715 AN XY: 487258

Gnomad4 AFR exome AF: 0.0478 AC: 1103 AN: 23054

Gnomad4 AMR exome AF: 0.0192 AC: 828 AN: 43016

Gnomad4 ASJ exome AF: 0.0253 AC: 565 AN: 22354

Gnomad4 EAS exome AF: 0.0292 AC: 1080 AN: 36952

Gnomad4 SAS exome AF: 0.0722 AC: 5339 AN: 73906

Gnomad4 FIN exome AF: 0.0729 AC: 3772 AN: 51758

Gnomad4 NFE exome AF: 0.0466 AC: 29662 AN: 635972

Gnomad4 Remaining exome AF: 0.0463 AC: 1984 AN: 42814

GnomAD4 genome AF: 0.0471 AC: 7162 AN: 152114 Hom.: 192 Cov.: 32 AF XY: 0.0481 AC XY: 3573 AN XY: 74352

Gnomad4 AFR AF: 0.0461 AC: 0.0461461 AN: 0.0461461

Gnomad4 AMR AF: 0.0298 AC: 0.0297783 AN: 0.0297783

Gnomad4 ASJ AF: 0.0236 AC: 0.0236175 AN: 0.0236175

Gnomad4 EAS AF: 0.0422 AC: 0.0421687 AN: 0.0421687

Gnomad4 SAS AF: 0.0746 AC: 0.0745959 AN: 0.0745959

Gnomad4 FIN AF: 0.0744 AC: 0.0743778 AN: 0.0743778

Gnomad4 NFE AF: 0.0472 AC: 0.0472245 AN: 0.0472245

Gnomad4 OTH AF: 0.0463 AC: 0.0463138 AN: 0.0463138

Alfa AF: 0.0450 Hom.: 65

Bravo AF: 0.0419

Asia WGS AF: 0.0590 AC: 206 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.85
BranchPoint Hunter		2.0
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs113385926; hg19: chr7-31848763;