16-4009438-T-C

Variant names:

• chr16-4009438-T-C
• rs2238448
• NM_001116.4:c.1694-1880A>G

Variant summary

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

The NM_001116.4(ADCY9):​c.1694-1880A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 151,948 control chromosomes in the GnomAD database, including 15,967 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 0.43 (15967 hom., cov: 32)
• Consequence: ADCY9 NM_001116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001116.4. 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
	ADCY9	NM_001116.4	MANE Select	c.1694-1880A>G		intron	N/A	NP_001107.2	O60503

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY9	ENST00000294016.8	TSL:1 MANE Select	c.1694-1880A>G		intron	N/A	ENSP00000294016.3	O60503
	ADCY9	ENST00000936467.1		c.1784-1880A>G		intron	N/A	ENSP00000606526.1
	ADCY9	ENST00000868252.1		c.1694-1880A>G		intron	N/A	ENSP00000538311.1

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65310 AN: 151830 Hom.: 15964 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.430 AC: 65311 AN: 151948 Hom.: 15967 Cov.: 32 AF XY: 0.434 AC XY: 32216 AN XY: 74248

African (AFR) AF: 0.185 AC: 7677 AN: 41462

American (AMR) AF: 0.417 AC: 6368 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1931 AN: 3468

East Asian (EAS) AF: 0.554 AC: 2850 AN: 5146

South Asian (SAS) AF: 0.460 AC: 2211 AN: 4804

European-Finnish (FIN) AF: 0.570 AC: 6017 AN: 10562

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36684 AN: 67932

Other (OTH) AF: 0.429 AC: 904 AN: 2108

Alfa AF: 0.372 Hom.: 4819

Bravo AF: 0.409

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.86
PhyloP100		0.26
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: rs2238448; hg19: chr16-4059439;