4-119501164-A-AAAT

Variant names:

• chr4-119501164-A-AAAT
• rs201238414
• NM_001083.4:c.2490+3_2490+5dupATT

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001083.4(PDE5A):​c.2490+3_2490+5dupATT variant causes a splice 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_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.789
• Publications: 1 publications found

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]

ENSG00000291203 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -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 VariationId is 722286.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 9 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083.4. 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
	PDE5A	NM_001083.4	MANE Select	c.2490+3_2490+5dupATT		splice_region intron	N/A	NP_001074.2	O76074-1
	PDE5A	NM_033430.3		c.2364+3_2364+5dupATT		splice_region intron	N/A	NP_236914.2	O76074-2
	PDE5A	NM_033437.4		c.2334+3_2334+5dupATT		splice_region intron	N/A	NP_246273.2	G5E9C5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.2490+3_2490+5dupATT		splice_region intron	N/A	ENSP00000347046.3	O76074-1
	PDE5A	ENST00000264805.9	TSL:1	c.2364+3_2364+5dupATT		splice_region intron	N/A	ENSP00000264805.5	O76074-2
	PDE5A	ENST00000503412.1	TSL:3	c.546_548dupATT	p.Val182_Phe183insLeu	disruptive_inframe_insertion	Exon 7 of 7	ENSP00000425810.1	H0YA14

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

GnomAD2 exomes AF: 0.00106 AC: 265 AN: 250358 AF XY: 0.000746

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 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

African (AFR) AF: 0.0156 AC: 510 AN: 32664

American (AMR) AF: 0.000896 AC: 40 AN: 44626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25868

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53250

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5702

European-Non Finnish (NFE) AF: 0.0000268 AC: 29 AN: 1080206

Other (OTH) AF: 0.000743 AC: 44 AN: 59180

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

African (AFR) AF: 0.0149 AC: 617 AN: 41544

American (AMR) AF: 0.00262 AC: 40 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68024

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

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

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
PhyloP100		0.79
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: rs201238414; hg19: chr4-120422319;