rs12061996

Variant names:

• chr1-167845147-A-G
• rs12061996
• NM_018417.6:c.3007+416T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

ADCY10 Gene-Disease associations (from GenCC):

• hypercalciuria, absorptive, 2

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• idiopathic inherited hypercalciuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.3007+416T>C		intron_variant	Intron 21 of 32	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.3007+416T>C		intron_variant	Intron 21 of 32	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.2731+416T>C		intron_variant	Intron 21 of 32	1		ENSP00000356822.1
ADCY10	ENST00000485964.5	n.697+416T>C		intron_variant	Intron 3 of 14	5		ENSP00000476402.1
ADCY10	ENST00000545172.5	c.2548+416T>C		intron_variant	Intron 18 of 29	2		ENSP00000441992.1

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

African (AFR) AF: 0.380 AC: 15758 AN: 41448

American (AMR) AF: 0.191 AC: 2920 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 396 AN: 3472

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5194

South Asian (SAS) AF: 0.0715 AC: 345 AN: 4822

European-Finnish (FIN) AF: 0.0287 AC: 305 AN: 10618

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.0678 AC: 4614 AN: 68004

Other (OTH) AF: 0.162 AC: 342 AN: 2112

Alfa AF: 0.113 Hom.: 4539

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
PhyloP100		-0.29
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: rs12061996; hg19: chr1-167814385;