rs215738

Variant names:

• chr7-32404823-G-A
• rs215738
• NM_001322059.2:c.310+22999C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-32404823-G-A
• chr7-32404823-G-C
• chr7-32404823-G-T

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+22999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 152,176 control chromosomes in the GnomAD database, including 57,139 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 0.85 (57139 hom., cov: 32)
• Consequence: PDE1C NM_001322059.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869
• Publications: 2 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 = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001322059.2	c.310+22999C>T		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+22999C>T		intron_variant	Intron 1 of 1			ENSP00000499831.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 129118 AN: 152058 Hom.: 57135 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.974

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.969

Gnomad OTH AF: 0.861

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

GnomAD4 genome AF: 0.849 AC: 129164 AN: 152176 Hom.: 57139 Cov.: 32 AF XY: 0.850 AC XY: 63263 AN XY: 74404

African (AFR) AF: 0.573 AC: 23754 AN: 41448

American (AMR) AF: 0.908 AC: 13881 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3215 AN: 3470

East Asian (EAS) AF: 0.992 AC: 5128 AN: 5170

South Asian (SAS) AF: 0.824 AC: 3973 AN: 4824

European-Finnish (FIN) AF: 0.974 AC: 10352 AN: 10626

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.969 AC: 65890 AN: 68030

Other (OTH) AF: 0.862 AC: 1817 AN: 2108

Alfa AF: 0.933 Hom.: 280927

Bravo AF: 0.833

Asia WGS AF: 0.879 AC: 3056 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	7.7
DANN	Benign	0.66
PhyloP100		0.87

Splicing

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

Other links and lift over

dbSNP: rs215738; hg19: chr7-32444435;