rs2863273

chr1-167834658-T-Achr1-167834658-T-Cchr1-167834658-T-G

Variant summary

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

The NM_018417.6(ADCY10):c.3310-581A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 168,714 control chromosomes in the GnomAD database, including 3,571 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 0.20 (3284 hom., cov: 32)
  • Exomes 𝑓: 0.17 (287 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

Genes affected

ADCY10 (HGNC:21285): (adenylate cyclase 10) The protein encoded by this gene belongs to a distinct class of adenylyl cyclases that is soluble and insensitive to G protein or forskolin regulation. Activity of this protein is regulated by bicarbonate. Variation at this gene has been observed in patients with absorptive hypercalciuria. Alternatively spliced transcript variants encoding different isoforms have been observed. There is a pseudogene of this gene on chromosome 6. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.3310-581A>T		intron_variant		ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.3310-581A>T		intron_variant		1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.3034-581A>T		intron_variant		1
ADCY10	ENST00000545172.5	c.2851-581A>T		intron_variant		2
ADCY10	ENST00000485964.5	c.737A>T	p.Tyr246Phe	missense_variant, NMD_transcript_variant	4/15	5

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31088 AN: 151918 Hom.: 3284 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.216

GnomAD3 exomes AF: 0.161 AC: 986 AN: 6120 Hom.: 78 AF XY: 0.165 AC XY: 571 AN XY: 3454

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.169

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.166 AC: 2768 AN: 16678 Hom.: 287 Cov.: 0 AF XY: 0.170 AC XY: 1466 AN XY: 8642

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.183

Gnomad4 ASJ exome AF: 0.234

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.0926

Gnomad4 NFE exome AF: 0.147

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.205 AC: 31115 AN: 152036 Hom.: 3284 Cov.: 32 AF XY: 0.205 AC XY: 15220 AN XY: 74310

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.215

Alfa AF: 0.179 Hom.: 348

Bravo AF: 0.213

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.37

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: rs2863273; hg19: chr1-167803896;