rs12061996

chr1-167845147-A-G

Variant summary

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

The NM_018417.6(ADCY10):c.3007+416T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 152,162 control chromosomes in the GnomAD database, including 3,509 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 0.16 (3509 hom., cov: 32)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.3007+416T>C		intron_variant		ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.3007+416T>C		intron_variant		1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.2731+416T>C		intron_variant		1
ADCY10	ENST00000545172.5	c.2548+416T>C		intron_variant		2
ADCY10	ENST00000485964.5	c.699+416T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24826 AN: 152044 Hom.: 3497 Cov.: 32

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0711

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0679

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.163 AC: 24877 AN: 152162 Hom.: 3509 Cov.: 32 AF XY: 0.162 AC XY: 12024 AN XY: 74428

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.0133

Gnomad4 SAS AF: 0.0715

Gnomad4 FIN AF: 0.0287

Gnomad4 NFE AF: 0.0678

Gnomad4 OTH AF: 0.162

Alfa AF: 0.127 Hom.: 971

Bravo AF: 0.186

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.044
Dann	Benign	0.43

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: rs12061996; hg19: chr1-167814385;