rs3767457

Positions:

• chr1-167852975-T-C
• chr1-167852975-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018417.6(ADCY10):​c.2308+1378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 151,910 control chromosomes in the GnomAD database, including 5,445 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 0.26 (5445 hom., cov: 31)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.684

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.2308+1378A>G		intron_variant		ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.2308+1378A>G		intron_variant		1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.2032+1378A>G		intron_variant		1
ADCY10	ENST00000545172.5	c.1849+1378A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40054 AN: 151792 Hom.: 5438 Cov.: 31

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.264 AC: 40073 AN: 151910 Hom.: 5445 Cov.: 31 AF XY: 0.259 AC XY: 19243 AN XY: 74232

Gnomad4 AFR AF: 0.201

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.257

Alfa AF: 0.284 Hom.: 8308

Bravo AF: 0.262

Asia WGS AF: 0.272 AC: 945 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.4
DANN	Benign	0.97

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

Publications

LitVar

Other links and lift over

dbSNP: rs3767457; hg19: chr1-167822213;