rs10775349

Positions:

• chr16-4029822-G-C

Variant summary

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

The NM_001116.4(ADCY9):​c.1694-22264C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,154 control chromosomes in the GnomAD database, including 43,621 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 0.71 (43621 hom., cov: 32)
• Consequence: ADCY9 NM_001116.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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]

ADCY9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY9	NM_001116.4	c.1694-22264C>G		intron_variant		ENST00000294016.8	NP_001107.2
ADCY9	XM_005255079.4	c.1694-22264C>G		intron_variant			XP_005255136.1
ADCY9	XM_011522353.3	c.1694-22264C>G		intron_variant			XP_011520655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY9	ENST00000294016.8	c.1694-22264C>G		intron_variant		1	NM_001116.4	ENSP00000294016.3
ADCY9	ENST00000572288.1	c.278-22264C>G		intron_variant		4		ENSP00000461825.1
ADCY9	ENST00000571467.1	n.176-36312C>G		intron_variant		5		ENSP00000460160.1
ADCY9	ENST00000571889.1	n.157-22264C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108026 AN: 152038 Hom.: 43620 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.824

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.912

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.886

Gnomad OTH AF: 0.759

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

GnomAD4 genome AF: 0.710 AC: 108050 AN: 152154 Hom.: 43621 Cov.: 32 AF XY: 0.716 AC XY: 53268 AN XY: 74378

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.750

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.912

Gnomad4 FIN AF: 0.890

Gnomad4 NFE AF: 0.886

Gnomad4 OTH AF: 0.762

Alfa AF: 0.782 Hom.: 6233

Bravo AF: 0.678

Asia WGS AF: 0.883 AC: 3071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.86

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: rs10775349; hg19: chr16-4079823;