NM_018417.6:c.4671+97T>G

Variant names:

• chr1-167810628-A-C
• rs74486783
• NM_018417.6:c.4671+97T>G

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.4671+97T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 1,141,038 control chromosomes in the GnomAD database, including 4,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (424 hom., cov: 32)
  • Exomes 𝑓: 0.082 (3746 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.164
• Publications: 2 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=-0.85).
• BP6: Variant 1-167810628-A-C is Benign according to our data. Variant chr1-167810628-A-C is described in ClinVar as Benign. ClinVar VariationId is 1248268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 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.4671+97T>G		intron	N/A	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.4395+97T>G		intron	N/A	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.4212+97T>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.4671+97T>G		intron	N/A	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.4395+97T>G		intron	N/A	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000485964.5	TSL:5	n.*1607+97T>G		intron	N/A	ENSP00000476402.1	V9GY51

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10871 AN: 152106 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0428

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0822

GnomAD4 exome AF: 0.0817 AC: 80780 AN: 988814 Hom.: 3746 AF XY: 0.0846 AC XY: 42928 AN XY: 507636

African (AFR) AF: 0.0571 AC: 1384 AN: 24238

American (AMR) AF: 0.0427 AC: 1598 AN: 37412

Ashkenazi Jewish (ASJ) AF: 0.0948 AC: 2160 AN: 22794

East Asian (EAS) AF: 0.0439 AC: 1597 AN: 36342

South Asian (SAS) AF: 0.139 AC: 10073 AN: 72418

European-Finnish (FIN) AF: 0.0758 AC: 3751 AN: 49458

Middle Eastern (MID) AF: 0.111 AC: 506 AN: 4572

European-Non Finnish (NFE) AF: 0.0804 AC: 56042 AN: 696704

Other (OTH) AF: 0.0818 AC: 3669 AN: 44876

GnomAD4 genome AF: 0.0714 AC: 10867 AN: 152224 Hom.: 424 Cov.: 32 AF XY: 0.0710 AC XY: 5281 AN XY: 74426

African (AFR) AF: 0.0587 AC: 2440 AN: 41534

American (AMR) AF: 0.0535 AC: 819 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 355 AN: 3472

East Asian (EAS) AF: 0.0425 AC: 220 AN: 5172

South Asian (SAS) AF: 0.145 AC: 699 AN: 4826

European-Finnish (FIN) AF: 0.0730 AC: 774 AN: 10604

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0786 AC: 5345 AN: 68000

Other (OTH) AF: 0.0814 AC: 172 AN: 2114

Alfa AF: 0.0752 Hom.: 667

Bravo AF: 0.0693

Asia WGS AF: 0.0850 AC: 297 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	-0.85
CADD	Benign	4.1
DANN	Benign	0.72
PhyloP100		0.16
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: rs74486783; hg19: chr1-167779865; COSMIC: COSV63242383;