rs4893975

Variant names:

• chr2-177656018-A-G
• rs4893975
• NM_016953.4:c.2646+7848T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016953.4(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 NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016953.4. 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
	PDE11A	NM_016953.4	MANE Select	c.2646+7848T>C		intron	N/A	NP_058649.3
	PDE11A	NM_001077197.2		c.1896+7848T>C		intron	N/A	NP_001070665.1	Q9HCR9-2
	PDE11A	NM_001077358.2		c.1572+7848T>C		intron	N/A	NP_001070826.1	Q9HCR9-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE11A	ENST00000286063.11	TSL:1 MANE Select	c.2646+7848T>C		intron	N/A	ENSP00000286063.5	Q9HCR9-1
	PDE11A	ENST00000358450.8	TSL:1	c.1896+7848T>C		intron	N/A	ENSP00000351232.4	Q9HCR9-2
	PDE11A	ENST00000409504.5	TSL:1	c.1572+7848T>C		intron	N/A	ENSP00000386539.1	Q9HCR9-3

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

African (AFR) AF: 0.631 AC: 26152 AN: 41438

American (AMR) AF: 0.836 AC: 12783 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2656 AN: 3468

East Asian (EAS) AF: 0.895 AC: 4636 AN: 5182

South Asian (SAS) AF: 0.882 AC: 4255 AN: 4826

European-Finnish (FIN) AF: 0.852 AC: 9016 AN: 10580

Middle Eastern (MID) AF: 0.810 AC: 238 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55436 AN: 67980

Other (OTH) AF: 0.774 AC: 1634 AN: 2110

Alfa AF: 0.779 Hom.: 7073

Bravo AF: 0.762

Asia WGS AF: 0.871 AC: 3025 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.9
DANN	Benign	0.67
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs4893975; hg19: chr2-178520746;