chr4-119542701-A-T

Variant names:

• chr4-119542701-A-T
• rs2622497
• NM_001083.4:c.1397-67T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001083.4(PDE5A):​c.1397-67T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE5A NM_001083.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 5 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	NM_001083.4	MANE Select	c.1397-67T>A		intron	N/A	NP_001074.2
	PDE5A	NM_033430.3		c.1271-67T>A		intron	N/A	NP_236914.2
	PDE5A	NM_033437.4		c.1241-67T>A		intron	N/A	NP_246273.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE5A	ENST00000354960.8	TSL:1 MANE Select	c.1397-67T>A		intron	N/A	ENSP00000347046.3
	PDE5A	ENST00000264805.9	TSL:1	c.1271-67T>A		intron	N/A	ENSP00000264805.5
	ENSG00000291203	ENST00000500559.6	TSL:1	n.251-7678A>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1235896 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 619212

African (AFR) AF: 0.00 AC: 0 AN: 29230

American (AMR) AF: 0.00 AC: 0 AN: 42396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22802

East Asian (EAS) AF: 0.00 AC: 0 AN: 38352

South Asian (SAS) AF: 0.00 AC: 0 AN: 75764

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51700

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 917780

Other (OTH) AF: 0.00 AC: 0 AN: 52618

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.14
PhyloP100		-0.63

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2622497; hg19: chr4-120463856;