7-32421112-G-T

Variant names:

• chr7-32421112-G-T
• rs62458065
• NM_001322059.2:c.310+6710C>A

Variant summary

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

The NM_001322059.2(PDE1C):​c.310+6710C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 144,402 control chromosomes in the GnomAD database, including 2,754 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 0.19 (2754 hom., cov: 32)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001322059.2	c.310+6710C>A		intron_variant	Intron 1 of 17		NP_001308988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE1C	ENST00000672256.1	c.310+6710C>A		intron_variant	Intron 1 of 1			ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 28042 AN: 144288 Hom.: 2744 Cov.: 32

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.0306

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.195 AC: 28094 AN: 144402 Hom.: 2754 Cov.: 32 AF XY: 0.194 AC XY: 13614 AN XY: 70276

African (AFR) AF: 0.252 AC: 10107 AN: 40150

American (AMR) AF: 0.181 AC: 2577 AN: 14234

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 448 AN: 3286

East Asian (EAS) AF: 0.310 AC: 1531 AN: 4942

South Asian (SAS) AF: 0.172 AC: 772 AN: 4490

European-Finnish (FIN) AF: 0.151 AC: 1438 AN: 9548

Middle Eastern (MID) AF: 0.150 AC: 41 AN: 274

European-Non Finnish (NFE) AF: 0.166 AC: 10752 AN: 64624

Other (OTH) AF: 0.201 AC: 402 AN: 2004

Alfa AF: 0.195 Hom.: 693

Bravo AF: 0.190

Asia WGS AF: 0.264 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.068
DANN	Benign	0.48
PhyloP100		-2.0

Splicing

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

Other links and lift over

dbSNP: rs62458065; hg19: chr7-32460724;