rs2269679

Variant names:

• chr1-167846372-C-A
• rs2269679
• NM_018417.6:c.2438-109G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-167846372-C-A
• chr1-167846372-C-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.2438-109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,383,640 control chromosomes in the GnomAD database, including 87,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7955 hom., cov: 32)
  • Exomes 𝑓: 0.36 (79389 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.214
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-167846372-C-A is Benign according to our data. Variant chr1-167846372-C-A is described in ClinVar as Benign. ClinVar VariationId is 1183578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	NM_018417.6	MANE Select	c.2438-109G>T		intron	N/A	NP_060887.2
	ADCY10	NM_001297772.2		c.2162-109G>T		intron	N/A	NP_001284701.1
	ADCY10	NM_001167749.3		c.1979-109G>T		intron	N/A	NP_001161221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.2438-109G>T		intron	N/A	ENSP00000356825.4
	ADCY10	ENST00000367848.1	TSL:1	c.2162-109G>T		intron	N/A	ENSP00000356822.1
	ADCY10	ENST00000485964.5	TSL:5	n.128-109G>T		intron	N/A	ENSP00000476402.1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48277 AN: 151944 Hom.: 7951 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.357 AC: 439224 AN: 1231578 Hom.: 79389 AF XY: 0.353 AC XY: 219544 AN XY: 621928

African (AFR) AF: 0.217 AC: 6160 AN: 28358

American (AMR) AF: 0.363 AC: 14798 AN: 40736

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 9939 AN: 24316

East Asian (EAS) AF: 0.438 AC: 16435 AN: 37548

South Asian (SAS) AF: 0.253 AC: 20180 AN: 79694

European-Finnish (FIN) AF: 0.333 AC: 17224 AN: 51736

Middle Eastern (MID) AF: 0.198 AC: 953 AN: 4804

European-Non Finnish (NFE) AF: 0.368 AC: 335301 AN: 911660

Other (OTH) AF: 0.346 AC: 18234 AN: 52726

GnomAD4 genome AF: 0.318 AC: 48289 AN: 152062 Hom.: 7955 Cov.: 32 AF XY: 0.315 AC XY: 23379 AN XY: 74312

African (AFR) AF: 0.231 AC: 9599 AN: 41474

American (AMR) AF: 0.347 AC: 5294 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1389 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2240 AN: 5176

South Asian (SAS) AF: 0.251 AC: 1212 AN: 4822

European-Finnish (FIN) AF: 0.325 AC: 3433 AN: 10554

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

European-Non Finnish (NFE) AF: 0.356 AC: 24183 AN: 67976

Other (OTH) AF: 0.318 AC: 672 AN: 2112

Alfa AF: 0.341 Hom.: 4558

Bravo AF: 0.314

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.90
CADD	Benign	0.36
DANN	Benign	0.34
PhyloP100		-0.21
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: rs2269679; hg19: chr1-167815610; COSMIC: COSV63241697;