rs7512378

Variant names:

• chr1-167855896-A-G
• rs7512378
• NM_018417.6:c.2171+269T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-167855896-A-G
• chr1-167855896-A-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018417.6(ADCY10):​c.2171+269T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,968 control chromosomes in the GnomAD database, including 5,636 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.27 (5636 hom., cov: 32)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.07
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BP6: Variant 1-167855896-A-G is Benign according to our data. Variant chr1-167855896-A-G is described in ClinVar as Benign. ClinVar VariationId is 1269849.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.278 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.2171+269T>C		intron	N/A	NP_060887.2	Q96PN6-1
	ADCY10	NM_001297772.2		c.1895+269T>C		intron	N/A	NP_001284701.1	Q96PN6-2
	ADCY10	NM_001167749.3		c.1712+269T>C		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.2171+269T>C		intron	N/A	ENSP00000356825.4	Q96PN6-1
	ADCY10	ENST00000367848.1	TSL:1	c.1895+269T>C		intron	N/A	ENSP00000356822.1	Q96PN6-2
	ADCY10	ENST00000545172.5	TSL:2	c.1712+269T>C		intron	N/A	ENSP00000441992.1	Q96PN6-4

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41134 AN: 151850 Hom.: 5628 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.271 AC: 41161 AN: 151968 Hom.: 5636 Cov.: 32 AF XY: 0.266 AC XY: 19756 AN XY: 74256

African (AFR) AF: 0.282 AC: 11671 AN: 41438

American (AMR) AF: 0.271 AC: 4141 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1212 AN: 5164

South Asian (SAS) AF: 0.160 AC: 770 AN: 4800

European-Finnish (FIN) AF: 0.257 AC: 2716 AN: 10556

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.281 AC: 19123 AN: 67950

Other (OTH) AF: 0.240 AC: 507 AN: 2114

Alfa AF: 0.274 Hom.: 21893

Bravo AF: 0.271

Asia WGS AF: 0.230 AC: 802 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.22
DANN	Benign	0.30
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs7512378; hg19: chr1-167825134;