rs2072338

Variant names:

• chr16-4006926-A-G
• rs2072338
• NM_001116.4:c.1884+442T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001116.4(ADCY9):​c.1884+442T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0886 in 152,190 control chromosomes in the GnomAD database, including 840 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 0.089 (840 hom., cov: 32)
• Consequence: ADCY9 NM_001116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.74
• Publications: 3 publications found

Genes affected

ADCY9 (HGNC:240): (adenylate cyclase 9) Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. It is regulated by a family of G protein-coupled receptors, protein kinases, and calcium. The type 9 adenylyl cyclase is a widely distributed adenylyl cyclase, and it is stimulated by beta-adrenergic receptor activation but is insensitive to forskolin, calcium, and somatostatin. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY9	NM_001116.4	c.1884+442T>C		intron_variant	Intron 3 of 10	ENST00000294016.8	NP_001107.2
ADCY9	XM_005255079.4	c.1884+442T>C		intron_variant	Intron 3 of 10		XP_005255136.1
ADCY9	XM_011522353.3	c.1884+442T>C		intron_variant	Intron 3 of 10		XP_011520655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY9	ENST00000294016.8	c.1884+442T>C		intron_variant	Intron 3 of 10	1	NM_001116.4	ENSP00000294016.3

Frequencies

GnomAD3 genomes AF: 0.0885 AC: 13458 AN: 152072 Hom.: 840 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0535

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.0886 AC: 13486 AN: 152190 Hom.: 840 Cov.: 32 AF XY: 0.0919 AC XY: 6840 AN XY: 74416

African (AFR) AF: 0.112 AC: 4634 AN: 41518

American (AMR) AF: 0.103 AC: 1577 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.296 AC: 1529 AN: 5166

South Asian (SAS) AF: 0.245 AC: 1180 AN: 4820

European-Finnish (FIN) AF: 0.0507 AC: 538 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0535 AC: 3639 AN: 68010

Other (OTH) AF: 0.0952 AC: 201 AN: 2112

Alfa AF: 0.0670 Hom.: 891

Bravo AF: 0.0906

Asia WGS AF: 0.314 AC: 1094 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		1.7
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: rs2072338; hg19: chr16-4056927;