chr7-31775671-C-G

Variant names:

• chr7-31775671-C-G
• rs79948907
• NM_001191057.4:c.1953G>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001191057.4(PDE1C):​c.1953G>C​(p.Thr651Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00574 in 1,612,494 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (34 hom.)
• Consequence: PDE1C NM_001191057.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.975
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-31775671-C-G is Benign according to our data. Variant chr7-31775671-C-G is described in ClinVar as Benign. ClinVar VariationId is 773211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.975 with no splicing effect.
• BS2: High AC in GnomAd4 at 1223 AD,Unknown gene.

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.1953G>C	p.Thr651Thr	synonymous	Exon 17 of 18	NP_001177986.1	Q14123-1
	PDE1C	NM_001191058.4		c.2133G>C	p.Thr711Thr	synonymous	Exon 18 of 19	NP_001177987.2	A0A0A0MS69
	PDE1C	NM_001191059.4		c.1953G>C	p.Thr651Thr	synonymous	Exon 18 of 19	NP_001177988.1	Q14123-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE1C	ENST00000396191.6	TSL:2 MANE Select	c.1953G>C	p.Thr651Thr	synonymous	Exon 17 of 18	ENSP00000379494.1	Q14123-1
	PDE1C	ENST00000396193.5	TSL:2	c.2133G>C	p.Thr711Thr	synonymous	Exon 18 of 19	ENSP00000379496.1	A0A0A0MS69
	PDE1C	ENST00000321453.12	TSL:2	c.1953G>C	p.Thr651Thr	synonymous	Exon 18 of 19	ENSP00000318105.7	Q14123-1

Frequencies

GnomAD3 genomes AF: 0.00800 AC: 1216 AN: 152044 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00246

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00723

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00437 AC: 1055 AN: 241476 AF XY: 0.00408

Gnomad AFR exome AF: 0.0133

Gnomad AMR exome AF: 0.00253

Gnomad ASJ exome AF: 0.00171

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00256

Gnomad NFE exome AF: 0.00621

Gnomad OTH exome AF: 0.00586

GnomAD4 exome AF: 0.00550 AC: 8028 AN: 1460332 Hom.: 34 Cov.: 30 AF XY: 0.00532 AC XY: 3866 AN XY: 726458

African (AFR) AF: 0.0153 AC: 512 AN: 33476

American (AMR) AF: 0.00266 AC: 119 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00180 AC: 47 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86230

European-Finnish (FIN) AF: 0.00266 AC: 139 AN: 52300

Middle Eastern (MID) AF: 0.00243 AC: 14 AN: 5768

European-Non Finnish (NFE) AF: 0.00615 AC: 6833 AN: 1111656

Other (OTH) AF: 0.00583 AC: 352 AN: 60352

GnomAD4 genome AF: 0.00804 AC: 1223 AN: 152162 Hom.: 7 Cov.: 32 AF XY: 0.00777 AC XY: 578 AN XY: 74400

African (AFR) AF: 0.0151 AC: 628 AN: 41514

American (AMR) AF: 0.00386 AC: 59 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00246 AC: 26 AN: 10588

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

European-Non Finnish (NFE) AF: 0.00723 AC: 492 AN: 68010

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.00347 Hom.: 0

Bravo AF: 0.00849

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.00687

EpiControl AF: 0.00658

ClinVar

ClinVar submissions

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	-0.50
CADD	Benign	0.33
DANN	Benign	0.54
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs79948907; hg19: chr7-31815285;