rs1476075

Variant names:

• chr1-167825168-G-A
• rs1476075
• NM_018417.6:c.3751-313C>T

Variant summary

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

The NM_018417.6(ADCY10):​c.3751-313C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 152,082 control chromosomes in the GnomAD database, including 25,744 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 0.58 (25744 hom., cov: 33)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.3751-313C>T		intron_variant	Intron 26 of 32	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.3751-313C>T		intron_variant	Intron 26 of 32	1	NM_018417.6	ENSP00000356825.4
ADCY10	ENST00000367848.1	c.3475-313C>T		intron_variant	Intron 26 of 32	1		ENSP00000356822.1
ADCY10	ENST00000485964.5	n.*637-313C>T		intron_variant	Intron 7 of 14	5		ENSP00000476402.1
ADCY10	ENST00000545172.5	c.3292-313C>T		intron_variant	Intron 23 of 29	2		ENSP00000441992.1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87391 AN: 151964 Hom.: 25710 Cov.: 33

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.576

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.575 AC: 87487 AN: 152082 Hom.: 25744 Cov.: 33 AF XY: 0.571 AC XY: 42469 AN XY: 74336

African (AFR) AF: 0.668 AC: 27728 AN: 41490

American (AMR) AF: 0.569 AC: 8697 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1799 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1522 AN: 5174

South Asian (SAS) AF: 0.379 AC: 1823 AN: 4810

European-Finnish (FIN) AF: 0.576 AC: 6076 AN: 10556

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38061 AN: 67974

Other (OTH) AF: 0.545 AC: 1152 AN: 2114

Alfa AF: 0.558 Hom.: 82998

Bravo AF: 0.577

Asia WGS AF: 0.391 AC: 1357 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.65
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: rs1476075; hg19: chr1-167794406;