rs10247918

Variant names:

• chr7-31814781-A-G
• rs10247918
• NM_001191057.4:c.1813+1143T>C

Variant summary

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

The NM_001191057.4(PDE1C):​c.1813+1143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 149,900 control chromosomes in the GnomAD database, including 23,364 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 0.53 (23364 hom., cov: 25)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 7 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 (NFE) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	NM_001191057.4	c.1813+1143T>C		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.1813+1143T>C		intron_variant	Intron 15 of 17	2	NM_001191057.4	ENSP00000379494.1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 79232 AN: 149780 Hom.: 23354 Cov.: 25

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.657

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.529 AC: 79254 AN: 149900 Hom.: 23364 Cov.: 25 AF XY: 0.532 AC XY: 38817 AN XY: 72984

African (AFR) AF: 0.247 AC: 10058 AN: 40698

American (AMR) AF: 0.601 AC: 8953 AN: 14908

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1855 AN: 3456

East Asian (EAS) AF: 0.537 AC: 2719 AN: 5066

South Asian (SAS) AF: 0.523 AC: 2422 AN: 4628

European-Finnish (FIN) AF: 0.681 AC: 6988 AN: 10262

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.657 AC: 44399 AN: 67618

Other (OTH) AF: 0.538 AC: 1117 AN: 2076

Alfa AF: 0.592 Hom.: 17633

Bravo AF: 0.512

Asia WGS AF: 0.548 AC: 1903 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	0.72
DANN	Benign	0.43
PhyloP100		-1.1
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: rs10247918; hg19: chr7-31854395;