1-167834658-T-A

Variant names:

• chr1-167834658-T-A
• rs2863273
• ENST00000485964.5:n.734A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000485964.5(ADCY10):​n.734A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 168,714 control chromosomes in the GnomAD database, including 3,571 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 0.20 (3284 hom., cov: 32)
  • Exomes 𝑓: 0.17 (287 hom.)
• Consequence: ADCY10 ENST00000485964.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485964.5. 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.3310-581A>T		intron	N/A	NP_060887.2
	ADCY10	NM_001297772.2		c.3034-581A>T		intron	N/A	NP_001284701.1
	ADCY10	NM_001167749.3		c.2851-581A>T		intron	N/A	NP_001161221.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADCY10	ENST00000485964.5	TSL:5	n.734A>T		non_coding_transcript_exon	Exon 4 of 15	ENSP00000476402.1
	ADCY10	ENST00000367851.9	TSL:1 MANE Select	c.3310-581A>T		intron	N/A	ENSP00000356825.4
	ADCY10	ENST00000367848.1	TSL:1	c.3034-581A>T		intron	N/A	ENSP00000356822.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31088 AN: 151918 Hom.: 3284 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.216

GnomAD2 exomes AF: 0.161 AC: 986 AN: 6120 AF XY: 0.165

Gnomad AFR exome AF: 0.142

Gnomad AMR exome AF: 0.166

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.169

Gnomad FIN exome AF: 0.111

Gnomad NFE exome AF: 0.138

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.166 AC: 2768 AN: 16678 Hom.: 287 Cov.: 0 AF XY: 0.170 AC XY: 1466 AN XY: 8642

African (AFR) AF: 0.182 AC: 56 AN: 308

American (AMR) AF: 0.183 AC: 487 AN: 2666

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 37 AN: 158

East Asian (EAS) AF: 0.160 AC: 152 AN: 948

South Asian (SAS) AF: 0.167 AC: 292 AN: 1744

European-Finnish (FIN) AF: 0.0926 AC: 25 AN: 270

Middle Eastern (MID) AF: 0.244 AC: 394 AN: 1612

European-Non Finnish (NFE) AF: 0.147 AC: 1204 AN: 8168

Other (OTH) AF: 0.150 AC: 121 AN: 804

GnomAD4 genome AF: 0.205 AC: 31115 AN: 152036 Hom.: 3284 Cov.: 32 AF XY: 0.205 AC XY: 15220 AN XY: 74310

African (AFR) AF: 0.235 AC: 9751 AN: 41418

American (AMR) AF: 0.203 AC: 3108 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1067 AN: 3472

East Asian (EAS) AF: 0.232 AC: 1202 AN: 5178

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4820

European-Finnish (FIN) AF: 0.163 AC: 1722 AN: 10564

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12465 AN: 67986

Other (OTH) AF: 0.215 AC: 453 AN: 2110

Alfa AF: 0.179 Hom.: 348

Bravo AF: 0.213

Asia WGS AF: 0.211 AC: 734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.0
DANN	Benign	0.37
PhyloP100		-0.11
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: rs2863273; hg19: chr1-167803896;