19-10420824-G-C

Variant names:

• chr19-10420824-G-C
• rs78392044
• NM_001111307.2:c.60G>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001111307.2(PDE4A):​c.60G>C​(p.Arg20Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00161 in 1,587,724 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0074 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (17 hom.)
• Consequence: PDE4A NM_001111307.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.48
• Publications: 2 publications found

Genes affected

PDE4A (HGNC:8780): (phosphodiesterase 4A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 19-10420824-G-C is Benign according to our data. Variant chr19-10420824-G-C is described in ClinVar as Benign. ClinVar VariationId is 768971.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.48 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00745 (1134/152270) while in subpopulation AFR AF = 0.0243 (1008/41564). AF 95% confidence interval is 0.023. There are 12 homozygotes in GnomAd4. There are 502 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1134 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111307.2. 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
	PDE4A	NM_001111307.2	MANE Select	c.60G>C	p.Arg20Arg	synonymous	Exon 1 of 15	NP_001104777.1	P27815-1
	PDE4A	NM_001243121.2		c.254+2959G>C		intron	N/A	NP_001230050.1	P27815-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	ENST00000380702.7	TSL:1 MANE Select	c.60G>C	p.Arg20Arg	synonymous	Exon 1 of 15	ENSP00000370078.3	P27815-1
	PDE4A	ENST00000592685.5	TSL:1	c.254+2959G>C		intron	N/A	ENSP00000468507.1	P27815-7
	PDE4A	ENST00000937031.1		c.60G>C	p.Arg20Arg	synonymous	Exon 1 of 15	ENSP00000607090.1

Frequencies

GnomAD3 genomes AF: 0.00740 AC: 1126 AN: 152162 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.00766

GnomAD2 exomes AF: 0.00169 AC: 344 AN: 203312 AF XY: 0.00125

Gnomad AFR exome AF: 0.0213

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.000112

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000394

Gnomad OTH exome AF: 0.00271

GnomAD4 exome AF: 0.000995 AC: 1428 AN: 1435454 Hom.: 17 Cov.: 32 AF XY: 0.000958 AC XY: 684 AN XY: 714232

African (AFR) AF: 0.0247 AC: 779 AN: 31558

American (AMR) AF: 0.00254 AC: 111 AN: 43752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.00 AC: 0 AN: 37878

South Asian (SAS) AF: 0.0000711 AC: 6 AN: 84408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39772

Middle Eastern (MID) AF: 0.0105 AC: 60 AN: 5716

European-Non Finnish (NFE) AF: 0.000265 AC: 293 AN: 1107096

Other (OTH) AF: 0.00300 AC: 179 AN: 59638

GnomAD4 genome AF: 0.00745 AC: 1134 AN: 152270 Hom.: 12 Cov.: 32 AF XY: 0.00674 AC XY: 502 AN XY: 74450

African (AFR) AF: 0.0243 AC: 1008 AN: 41564

American (AMR) AF: 0.00464 AC: 71 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

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

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.000485 AC: 33 AN: 68000

Other (OTH) AF: 0.00758 AC: 16 AN: 2110

Alfa AF: 0.00324 Hom.: 0

Bravo AF: 0.00857

Asia WGS AF: 0.00203 AC: 8 AN: 3468

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	8.5
DANN	Benign	0.75
PhyloP100		2.5
PromoterAI		-0.0042	Neutral
Mutation Taster		=98/2	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs78392044; hg19: chr19-10531500; COSMIC: COSV104420712; COSMIC: COSV104420712;