rs1034463

Variant names:

• chr1-167837409-T-A
• rs1034463
• NM_018417.6:c.3008-91A>T

Your query was ambiguous. Multiple possible variants found:

• chr1-167837409-T-A
• chr1-167837409-T-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018417.6(ADCY10):​c.3008-91A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,203,410 control chromosomes in the GnomAD database, including 269,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40942 hom., cov: 32)
  • Exomes 𝑓: 0.66 (228599 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.718
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-167837409-T-A is Benign according to our data. Variant chr1-167837409-T-A is described in ClinVar as Benign. ClinVar VariationId is 1253001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 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.3008-91A>T		intron	N/A	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.2732-91A>T		intron	N/A	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.2549-91A>T		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.3008-91A>T		intron	N/A	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.2732-91A>T		intron	N/A	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000485964.5	TSL:5	n.698-2715A>T		intron	N/A	ENSP00000476402.1	V9GY51

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109938 AN: 152048 Hom.: 40875 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.657 AC: 691140 AN: 1051244 Hom.: 228599 AF XY: 0.653 AC XY: 351216 AN XY: 537522

African (AFR) AF: 0.912 AC: 22881 AN: 25096

American (AMR) AF: 0.767 AC: 29546 AN: 38538

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 16063 AN: 23244

East Asian (EAS) AF: 0.552 AC: 20019 AN: 36244

South Asian (SAS) AF: 0.594 AC: 44372 AN: 74734

European-Finnish (FIN) AF: 0.640 AC: 30677 AN: 47922

Middle Eastern (MID) AF: 0.589 AC: 2953 AN: 5016

European-Non Finnish (NFE) AF: 0.655 AC: 493729 AN: 753756

Other (OTH) AF: 0.662 AC: 30900 AN: 46694

GnomAD4 genome AF: 0.723 AC: 110065 AN: 152166 Hom.: 40942 Cov.: 32 AF XY: 0.718 AC XY: 53394 AN XY: 74368

African (AFR) AF: 0.904 AC: 37560 AN: 41530

American (AMR) AF: 0.733 AC: 11200 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2411 AN: 3472

East Asian (EAS) AF: 0.512 AC: 2652 AN: 5182

South Asian (SAS) AF: 0.598 AC: 2886 AN: 4824

European-Finnish (FIN) AF: 0.650 AC: 6863 AN: 10562

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.652 AC: 44308 AN: 67994

Other (OTH) AF: 0.702 AC: 1483 AN: 2114

Alfa AF: 0.690 Hom.: 4661

Bravo AF: 0.740

Asia WGS AF: 0.595 AC: 2070 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.56
DANN	Benign	0.55
PhyloP100		-0.72
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: rs1034463; hg19: chr1-167806647; COSMIC: COSV63239231;