rs3767457

Variant names:

• chr1-167852975-T-C
• rs3767457
• NM_018417.6:c.2308+1378A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-167852975-T-C
• chr1-167852975-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018417.6(ADCY10):​c.2308+1378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,910 control chromosomes in the GnomAD database, including 5,445 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 0.26 (5445 hom., cov: 31)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684
• Publications: 5 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018417.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	NM_018417.6	MANE Select	c.2308+1378A>G		intron	N/A	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.2032+1378A>G		intron	N/A	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.1849+1378A>G		intron	N/A	NP_001161221.1	Q96PN6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.2308+1378A>G		intron	N/A	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.2032+1378A>G		intron	N/A	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000545172.5	TSL:2	c.1849+1378A>G		intron	N/A	ENSP00000441992.1	Q96PN6-4

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40054 AN: 151792 Hom.: 5438 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.264 AC: 40073 AN: 151910 Hom.: 5445 Cov.: 31 AF XY: 0.259 AC XY: 19243 AN XY: 74232

African (AFR) AF: 0.201 AC: 8317 AN: 41420

American (AMR) AF: 0.287 AC: 4382 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3466

East Asian (EAS) AF: 0.324 AC: 1673 AN: 5170

South Asian (SAS) AF: 0.187 AC: 904 AN: 4822

European-Finnish (FIN) AF: 0.261 AC: 2745 AN: 10532

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20289 AN: 67936

Other (OTH) AF: 0.257 AC: 543 AN: 2110

Alfa AF: 0.285 Hom.: 18800

Bravo AF: 0.262

Asia WGS AF: 0.272 AC: 945 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.4
DANN	Benign	0.97
PhyloP100		-0.68
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: rs3767457; hg19: chr1-167822213;