rs4893975

Positions:

• chr2-177656018-A-G

Variant summary

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

The ENST00000286063.11(PDE11A):​c.2646+7848T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.773 in 152,072 control chromosomes in the GnomAD database, including 46,136 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 0.77 (46136 hom., cov: 31)
• Consequence: PDE11A ENST00000286063.11 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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]

PDE11A-AS1 (HGNC:40433): (PDE11A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE11A	NM_016953.4	c.2646+7848T>C		intron_variant		ENST00000286063.11	NP_058649.3
PDE11A	NM_001077196.2	c.1314+7848T>C		intron_variant			NP_001070664.1
PDE11A	NM_001077197.2	c.1896+7848T>C		intron_variant			NP_001070665.1
PDE11A	NM_001077358.2	c.1572+7848T>C		intron_variant			NP_001070826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE11A	ENST00000286063.11	c.2646+7848T>C		intron_variant		1	NM_016953.4	ENSP00000286063	P1
PDE11A-AS1	ENST00000653062.1	n.365+2235A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.773 AC: 117509 AN: 151954 Hom.: 46105 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.863

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.895

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.773 AC: 117593 AN: 152072 Hom.: 46136 Cov.: 31 AF XY: 0.778 AC XY: 57878 AN XY: 74364

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.836

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.895

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.774

Alfa AF: 0.783 Hom.: 6914

Bravo AF: 0.762

Asia WGS AF: 0.871 AC: 3025 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.9
DANN	Benign	0.67

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: rs4893975; hg19: chr2-178520746;