1-167821380-T-C

Variant names:

• chr1-167821380-T-C
• rs4656560
• NM_018417.6:c.4286+644A>G

Variant summary

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

The NM_018417.6(ADCY10):​c.4286+644A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 152,174 control chromosomes in the GnomAD database, including 30,944 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 0.63 (30944 hom., cov: 33)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• 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

ENSG00000232194 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.4286+644A>G		intron_variant	Intron 30 of 32	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.4286+644A>G		intron_variant	Intron 30 of 32	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000485964.5	n.*1172+644A>G		intron_variant	Intron 11 of 14	5		ENSP00000476402.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95592 AN: 152056 Hom.: 30903 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.599

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

GnomAD4 genome AF: 0.629 AC: 95695 AN: 152174 Hom.: 30944 Cov.: 33 AF XY: 0.623 AC XY: 46350 AN XY: 74396

African (AFR) AF: 0.770 AC: 31960 AN: 41504

American (AMR) AF: 0.613 AC: 9381 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2058 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1951 AN: 5166

South Asian (SAS) AF: 0.428 AC: 2069 AN: 4830

European-Finnish (FIN) AF: 0.591 AC: 6259 AN: 10588

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40091 AN: 68006

Other (OTH) AF: 0.598 AC: 1263 AN: 2112

Alfa AF: 0.593 Hom.: 43499

Bravo AF: 0.635

Asia WGS AF: 0.457 AC: 1587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.68
PhyloP100		-0.27
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: rs4656560; hg19: chr1-167790618;