NM_016953.4:c.2154-3135C>A

Variant names:

• chr2-177704346-G-T
• rs1465831
• NM_016953.4:c.2154-3135C>A

Variant summary

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

The NM_016953.4(PDE11A):​c.2154-3135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 151,898 control chromosomes in the GnomAD database, including 1,905 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 0.094 (1905 hom., cov: 31)
• Consequence: PDE11A NM_016953.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.225
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 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.2154-3135C>A		intron	N/A	NP_058649.3
	PDE11A	NM_001077197.2		c.1404-3135C>A		intron	N/A	NP_001070665.1	Q9HCR9-2
	PDE11A	NM_001077358.2		c.1080-3135C>A		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.2154-3135C>A		intron	N/A	ENSP00000286063.5	Q9HCR9-1
	PDE11A	ENST00000358450.8	TSL:1	c.1404-3135C>A		intron	N/A	ENSP00000351232.4	Q9HCR9-2
	PDE11A	ENST00000409504.5	TSL:1	c.1080-3135C>A		intron	N/A	ENSP00000386539.1	Q9HCR9-3

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14233 AN: 151780 Hom.: 1898 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0480

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00603

Gnomad FIN AF: 0.0168

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0657

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

GnomAD4 genome AF: 0.0939 AC: 14266 AN: 151898 Hom.: 1905 Cov.: 31 AF XY: 0.0913 AC XY: 6779 AN XY: 74282

African (AFR) AF: 0.294 AC: 12159 AN: 41342

American (AMR) AF: 0.0479 AC: 731 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00979 AC: 34 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5168

South Asian (SAS) AF: 0.00603 AC: 29 AN: 4808

European-Finnish (FIN) AF: 0.0168 AC: 178 AN: 10580

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 978 AN: 67948

Other (OTH) AF: 0.0651 AC: 137 AN: 2106

Alfa AF: 0.145 Hom.: 689

Bravo AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.21
PhyloP100		-0.23
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: rs1465831; hg19: chr2-178569074;