rs7785412

Variant names:

• chr7-31907224-G-A
• rs7785412
• NM_001191057.4:c.129-26364C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-31907224-G-A
• chr7-31907224-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001191057.4(PDE1C):​c.129-26364C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,078 control chromosomes in the GnomAD database, including 62,667 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (62667 hom., cov: 30)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191057.4	c.129-26364C>T		intron_variant	Intron 2 of 17	ENST00000396191.6	NP_001177986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000396191.6	c.129-26364C>T		intron_variant	Intron 2 of 17	2	NM_001191057.4	ENSP00000379494.1

Frequencies

GnomAD3 genomes AF: 0.901 AC: 136848 AN: 151960 Hom.: 62626 Cov.: 30

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.999

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.974

Gnomad FIN AF: 0.967

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.913

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.900 AC: 136946 AN: 152078 Hom.: 62667 Cov.: 30 AF XY: 0.903 AC XY: 67122 AN XY: 74336

African (AFR) AF: 0.714 AC: 29562 AN: 41414

American (AMR) AF: 0.954 AC: 14559 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3382 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 0.973 AC: 4698 AN: 4826

European-Finnish (FIN) AF: 0.967 AC: 10240 AN: 10592

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66210 AN: 68016

Other (OTH) AF: 0.913 AC: 1931 AN: 2114

Alfa AF: 0.897 Hom.: 5209

Bravo AF: 0.891

Asia WGS AF: 0.976 AC: 3396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.0
DANN	Benign	0.82
PhyloP100		-0.28
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: rs7785412; hg19: chr7-31946837;