1-167849779-T-C

Variant names:

• chr1-167849779-T-C
• rs3767451
• NM_018417.6:c.2309-1290A>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.2309-1290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,034 control chromosomes in the GnomAD database, including 7,832 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 0.31 (7832 hom., cov: 32)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• 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: 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 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.2309-1290A>G		intron	N/A	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.2033-1290A>G		intron	N/A	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.1850-1290A>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.2309-1290A>G		intron	N/A	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.2033-1290A>G		intron	N/A	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000545172.5	TSL:2	c.1850-1290A>G		intron	N/A	ENSP00000441992.1	Q96PN6-4

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47589 AN: 151916 Hom.: 7826 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.313 AC: 47599 AN: 152034 Hom.: 7832 Cov.: 32 AF XY: 0.310 AC XY: 23011 AN XY: 74320

African (AFR) AF: 0.207 AC: 8572 AN: 41458

American (AMR) AF: 0.346 AC: 5293 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1391 AN: 3470

East Asian (EAS) AF: 0.433 AC: 2232 AN: 5154

South Asian (SAS) AF: 0.247 AC: 1192 AN: 4820

European-Finnish (FIN) AF: 0.328 AC: 3462 AN: 10564

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24533 AN: 67974

Other (OTH) AF: 0.312 AC: 657 AN: 2106

Alfa AF: 0.332 Hom.: 10558

Bravo AF: 0.309

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		-0.45
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: rs3767451; hg19: chr1-167819017;