rs2601828

Positions:

• chr16-4053870-T-C

Variant summary

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

The ENST00000294016.8(ADCY9):​c.1694-46312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 151,960 control chromosomes in the GnomAD database, including 45,029 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 (45029 hom., cov: 29)
• Consequence: ADCY9 ENST00000294016.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.750

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]

LOC124900373 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY9	NM_001116.4	c.1694-46312A>G		intron_variant		ENST00000294016.8	NP_001107.2
LOC124900373	XR_007064957.1	n.587-49A>G		intron_variant, non_coding_transcript_variant
ADCY9	XM_005255079.4	c.1694-46312A>G		intron_variant			XP_005255136.1
ADCY9	XM_011522353.3	c.1694-46312A>G		intron_variant			XP_011520655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY9	ENST00000294016.8	c.1694-46312A>G		intron_variant		1	NM_001116.4	ENSP00000294016	P1
ADCY9	ENST00000572288.1	c.278-46312A>G		intron_variant		4		ENSP00000461825
ADCY9	ENST00000571467.1	c.176+59880A>G		intron_variant, NMD_transcript_variant		5		ENSP00000460160
ADCY9	ENST00000571889.1	n.156+165A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116452 AN: 151842 Hom.: 44983 Cov.: 29

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.791

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.767 AC: 116543 AN: 151960 Hom.: 45029 Cov.: 29 AF XY: 0.765 AC XY: 56791 AN XY: 74246

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.744

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.791

Gnomad4 FIN AF: 0.742

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.775

Alfa AF: 0.760 Hom.: 101575

Bravo AF: 0.756

Asia WGS AF: 0.735 AC: 2559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.2
DANN	Benign	0.51

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: rs2601828; hg19: chr16-4103871;