rs1405647

Variant names:

• chr2-177894135-A-C
• rs1405647
• NM_016953.4:c.1302+3923T>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016953.4(PDE11A):​c.1302+3923T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.45 in 151,894 control chromosomes in the GnomAD database, including 17,122 homozygotes. 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: 𝑓 0.45 (17122 hom., cov: 31)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

Genes affected

PDE11A (HGNC:8773): (phosphodiesterase 11A) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE11A	NM_016953.4	c.1302+3923T>G		intron_variant	Intron 4 of 19	ENST00000286063.11	NP_058649.3
PDE11A	NM_001077197.2	c.552+3923T>G		intron_variant	Intron 5 of 20		NP_001070665.1
PDE11A	NM_001077358.2	c.228+3923T>G		intron_variant	Intron 3 of 18		NP_001070826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.1302+3923T>G		intron_variant	Intron 4 of 19	1	NM_016953.4	ENSP00000286063.5

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68213 AN: 151776 Hom.: 17085 Cov.: 31

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.429

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.450 AC: 68304 AN: 151894 Hom.: 17122 Cov.: 31 AF XY: 0.443 AC XY: 32912 AN XY: 74220

Gnomad4 AFR AF: 0.674

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.426

Alfa AF: 0.459 Hom.: 3079

Bravo AF: 0.451

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.92
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs1405647; hg19: chr2-178758862;