XM_047420441.1:c.2055+36640C>T

Variant names:

• chr7-31674353-G-A
• rs2391996
• XM_047420441.1:c.2055+36640C>T

Variant summary

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

The XM_047420441.1(PDE1C):​c.2055+36640C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 152,050 control chromosomes in the GnomAD database, including 38,319 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 0.71 (38319 hom., cov: 33)
• Consequence: PDE1C XM_047420441.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE1C	XM_047420441.1	c.2055+36640C>T		intron_variant	Intron 18 of 19		XP_047276397.1
PDE1C	XM_047420442.1	c.2055+36640C>T		intron_variant	Intron 19 of 20		XP_047276398.1
PDE1C	XM_047420443.1	c.2055+36640C>T		intron_variant	Intron 19 of 20		XP_047276399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107371 AN: 151932 Hom.: 38314 Cov.: 33

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.708

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

GnomAD4 genome AF: 0.706 AC: 107409 AN: 152050 Hom.: 38319 Cov.: 33 AF XY: 0.706 AC XY: 52440 AN XY: 74302

African (AFR) AF: 0.608 AC: 25189 AN: 41448

American (AMR) AF: 0.757 AC: 11573 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2775 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4247 AN: 5180

South Asian (SAS) AF: 0.767 AC: 3700 AN: 4822

European-Finnish (FIN) AF: 0.663 AC: 7002 AN: 10560

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.746 AC: 50688 AN: 67974

Other (OTH) AF: 0.706 AC: 1490 AN: 2110

Alfa AF: 0.731 Hom.: 24935

Bravo AF: 0.710

Asia WGS AF: 0.712 AC: 2474 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.58
DANN	Benign	0.61
PhyloP100		-0.17

Splicing

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

Other links and lift over

dbSNP: rs2391996; hg19: chr7-31713967;