Variant chr4-119505936-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001083.4(PDE5A):c.2190-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,533,452 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 24 hom. )

Consequence

PDE5A
NM_001083.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008263

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.208

Variant links:

Genes affected

PDE5A (HGNC:8784): (phosphodiesterase 5A) This gene encodes a cGMP-binding, cGMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family. This phosphodiesterase specifically hydrolyzes cGMP to 5'-GMP. It is involved in the regulation of intracellular concentrations of cyclic nucleotides and is important for smooth muscle relaxation in the cardiovascular system. Alternative splicing of this gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

PDE5A links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-119505936-C-T is Benign according to our data. Variant chr4-119505936-C-T is described in ClinVar as [Benign]. Clinvar id is 777148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
PDE5A	NM_001083.4 linkuse as main transcript	c.2190-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000354960.8
PDE5A	NM_033430.3 linkuse as main transcript	c.2064-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
PDE5A	NM_033437.4 linkuse as main transcript	c.2034-4G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE5A	ENST00000354960.8 linkuse as main transcript	c.2190-4G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001083.4		O76074-1
	ENST00000688315.1 linkuse as main transcript	n.1004-6415C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00468

AC:

709

AN:

151582

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.00765

Gnomad ASJ

AF:

0.00578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00662

Gnomad OTH

AF:

0.00674

GnomAD3 exomes

AF:

0.00467

AC:

980

AN:

209884

Hom.:

AF XY:

0.00511

AC XY:

587

AN XY:

114940

show subpopulations

Gnomad AFR exome

AF:

0.000771

Gnomad AMR exome

AF:

0.00577

Gnomad ASJ exome

AF:

0.00579

Gnomad EAS exome

AF:

0.0000677

Gnomad SAS exome

AF:

0.00355

Gnomad FIN exome

AF:

0.000239

Gnomad NFE exome

AF:

0.00666

Gnomad OTH exome

AF:

0.00496

GnomAD4 exome

AF:

0.00609

AC:

8410

AN:

1381752

Hom.:

Cov.:

AF XY:

0.00600

AC XY:

4133

AN XY:

689232

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.00569

Gnomad4 ASJ exome

AF:

0.00487

Gnomad4 EAS exome

AF:

0.0000538

Gnomad4 SAS exome

AF:

0.00343

Gnomad4 FIN exome

AF:

0.000548

Gnomad4 NFE exome

AF:

0.00686

Gnomad4 OTH exome

AF:

0.00699

GnomAD4 genome

AF:

0.00467

AC:

709

AN:

151700

Hom.:

Cov.:

AF XY:

0.00444

AC XY:

329

AN XY:

74118

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00764

Gnomad4 ASJ

AF:

0.00578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00663

Gnomad4 OTH

AF:

0.00667

Alfa

AF:

0.00546

Hom.:

Bravo

AF:

0.00511

Asia WGS

AF:

0.00145

AC:

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.8

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000083

dbscSNV1_RF

Benign

0.0020

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over