1-167809606-G-A

Position:

• chr1-167809606-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018417.6(ADCY10):​c.*72C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 1,538,322 control chromosomes in the GnomAD database, including 140,724 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20867 hom., cov: 32)
  • Exomes 𝑓: 0.41 (119857 hom.)
• Consequence: ADCY10 NM_018417.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0450

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-167809606-G-A is Benign according to our data. Variant chr1-167809606-G-A is described in ClinVar as [Benign]. Clinvar id is 1250999.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.*72C>T		3_prime_UTR_variant	33/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.*72C>T		3_prime_UTR_variant	33/33	1	NM_018417.6	P1
ADCY10	ENST00000545172.5	c.*72C>T		3_prime_UTR_variant	30/30	2
ADCY10	ENST00000485964.5			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75438 AN: 151976 Hom.: 20824 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.483

GnomAD4 exome AF: 0.408 AC: 566029 AN: 1386228 Hom.: 119857 Cov.: 21 AF XY: 0.407 AC XY: 282317 AN XY: 694168

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.469

Gnomad4 EAS exome AF: 0.176

Gnomad4 SAS exome AF: 0.374

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.497 AC: 75533 AN: 152094 Hom.: 20867 Cov.: 32 AF XY: 0.492 AC XY: 36555 AN XY: 74348

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.401

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.484

Alfa AF: 0.421 Hom.: 28915

Bravo AF: 0.506

Asia WGS AF: 0.314 AC: 1094 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.7
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3213588; hg19: chr1-167778843; COSMIC: COSV63240022; COSMIC: COSV63240022;