NM_001083.4:c.2010T>C

Variant names:

• chr4-119511125-A-G
• rs199578826
• NM_001083.4:c.2010T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4 BP6_Moderate BP7

The NM_001083.4(PDE5A):​c.2010T>C​(p.His670His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000152 in 1,606,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: PDE5A NM_001083.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.33
• Publications: 0 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.242).
• BP6: Variant 4-119511125-A-G is Benign according to our data. Variant chr4-119511125-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2655054.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.34 with no splicing effect.

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.2010T>C	p.His670His	synonymous	Exon 15 of 21	NP_001074.2	O76074-1
	PDE5A	NM_033430.3		c.1884T>C	p.His628His	synonymous	Exon 15 of 21	NP_236914.2	O76074-2
	PDE5A	NM_033437.4		c.1854T>C	p.His618His	synonymous	Exon 15 of 21	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.2010T>C	p.His670His	synonymous	Exon 15 of 21	ENSP00000347046.3	O76074-1
	PDE5A	ENST00000264805.9	TSL:1	c.1884T>C	p.His628His	synonymous	Exon 15 of 21	ENSP00000264805.5	O76074-2
	PDE5A	ENST00000925607.1		c.2007T>C	p.His669His	synonymous	Exon 15 of 21	ENSP00000595666.1

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000172 AC: 43 AN: 250412 AF XY: 0.000133

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000407

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000141 AC: 205 AN: 1453786 Hom.: 0 Cov.: 27 AF XY: 0.000151 AC XY: 109 AN XY: 723600

African (AFR) AF: 0.00 AC: 0 AN: 33268

American (AMR) AF: 0.000425 AC: 19 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.000152 AC: 13 AN: 85728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53326

Middle Eastern (MID) AF: 0.000871 AC: 5 AN: 5740

European-Non Finnish (NFE) AF: 0.000129 AC: 143 AN: 1105428

Other (OTH) AF: 0.000400 AC: 24 AN: 60052

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152254 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74454

African (AFR) AF: 0.0000241 AC: 1 AN: 41562

American (AMR) AF: 0.000982 AC: 15 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 68006

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.000360 Hom.: 1

Bravo AF: 0.000306

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.56
CADD	Benign	7.6
DANN	Benign	0.81
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199578826; hg19: chr4-120432280;