4-119501164-A-AAAT

Position:

• chr4-119501164-A-AAAT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001083.4(PDE5A):​c.2490+5_2490+6insATT variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000819 in 1,578,644 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0044 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (2 hom.)
• Consequence: PDE5A NM_001083.4 splice_donor_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.789

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 4-119501164-A-AAAT is Benign according to our data. Variant chr4-119501164-A-AAAT is described in ClinVar as [Benign]. Clinvar id is 722286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE5A	NM_001083.4	c.2490+5_2490+6insATT		splice_donor_region_variant, intron_variant		ENST00000354960.8	NP_001074.2
PDE5A	NM_033430.3	c.2364+5_2364+6insATT		splice_donor_region_variant, intron_variant			NP_236914.2
PDE5A	NM_033437.4	c.2334+5_2334+6insATT		splice_donor_region_variant, intron_variant			NP_246273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE5A	ENST00000354960.8	c.2490+5_2490+6insATT		splice_donor_region_variant, intron_variant		1	NM_001083.4	ENSP00000347046
	ENST00000688315.1	n.1003+3263_1003+3265dup		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 666 AN: 152142 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00106 AC: 265 AN: 250358 Hom.: 1 AF XY: 0.000746 AC XY: 101 AN XY: 135316

Gnomad AFR exome AF: 0.0145

Gnomad AMR exome AF: 0.000669

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000265

Gnomad OTH exome AF: 0.000492

GnomAD4 exome AF: 0.000439 AC: 626 AN: 1426384 Hom.: 2 Cov.: 25 AF XY: 0.000375 AC XY: 267 AN XY: 711786

Gnomad4 AFR exome AF: 0.0156

Gnomad4 AMR exome AF: 0.000896

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000268

Gnomad4 OTH exome AF: 0.000743

GnomAD4 genome AF: 0.00438 AC: 667 AN: 152260 Hom.: 9 Cov.: 32 AF XY: 0.00447 AC XY: 333 AN XY: 74448

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.00262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00190 Hom.: 0

Bravo AF: 0.00497

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000595

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs201238414; hg19: chr4-120422319;