rs73319150

Variant names:

• chr7-31815781-A-G
• rs73319150
• NM_001191057.4:c.1813+143T>C

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.1813+143T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00572 in 671,590 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (72 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (27 hom.)
• Consequence: PDE1C NM_001191057.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.434
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-31815781-A-G is Benign according to our data. Variant chr7-31815781-A-G is described in ClinVar as Benign. ClinVar VariationId is 1286911.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191057.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	NM_001191057.4	MANE Select	c.1813+143T>C		intron	N/A	NP_001177986.1	Q14123-1
	PDE1C	NM_001191058.4		c.1993+143T>C		intron	N/A	NP_001177987.2	A0A0A0MS69
	PDE1C	NM_001322059.2		c.2218+143T>C		intron	N/A	NP_001308988.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	ENST00000396191.6	TSL:2 MANE Select	c.1813+143T>C		intron	N/A	ENSP00000379494.1	Q14123-1
	PDE1C	ENST00000396182.6	TSL:1	c.1813+143T>C		intron	N/A	ENSP00000379485.2	Q14123-2
	PDE1C	ENST00000396184.7	TSL:1	c.1813+143T>C		intron	N/A	ENSP00000379487.3	Q14123-2

Frequencies

GnomAD3 genomes AF: 0.0177 AC: 2690 AN: 152048 Hom.: 72 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00485

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.00221 AC: 1147 AN: 519424 Hom.: 27 AF XY: 0.00184 AC XY: 509 AN XY: 277122

African (AFR) AF: 0.0586 AC: 845 AN: 14418

American (AMR) AF: 0.00260 AC: 63 AN: 24188

Ashkenazi Jewish (ASJ) AF: 0.000879 AC: 13 AN: 14796

East Asian (EAS) AF: 0.0000293 AC: 1 AN: 34156

South Asian (SAS) AF: 0.000177 AC: 9 AN: 50720

European-Finnish (FIN) AF: 0.0000250 AC: 1 AN: 40068

Middle Eastern (MID) AF: 0.00162 AC: 6 AN: 3704

European-Non Finnish (NFE) AF: 0.000291 AC: 90 AN: 308784

Other (OTH) AF: 0.00416 AC: 119 AN: 28590

GnomAD4 genome AF: 0.0177 AC: 2692 AN: 152166 Hom.: 72 Cov.: 32 AF XY: 0.0176 AC XY: 1309 AN XY: 74406

African (AFR) AF: 0.0618 AC: 2566 AN: 41532

American (AMR) AF: 0.00484 AC: 74 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 67986

Other (OTH) AF: 0.00945 AC: 20 AN: 2116

Alfa AF: 0.0146 Hom.: 2

Bravo AF: 0.0203

Asia WGS AF: 0.00260 AC: 10 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism

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: rs73319150; hg19: chr7-31855395;