1-167809468-A-C

Position:

• chr1-167809468-A-C

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.*210T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 583,956 control chromosomes in the GnomAD database, including 6,316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1567 hom., cov: 33)
  • Exomes 𝑓: 0.14 (4749 hom.)
• Consequence: ADCY10 NM_018417.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.507

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=-0.9).
• BP6: Variant 1-167809468-A-C is Benign according to our data. Variant chr1-167809468-A-C is described in ClinVar as [Benign]. Clinvar id is 1232117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.*210T>G		3_prime_UTR_variant	33/33	ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.*210T>G		3_prime_UTR_variant	33/33	1	NM_018417.6	ENSP00000356825	P1
ADCY10	ENST00000545172.5	c.*210T>G		3_prime_UTR_variant	30/30	2		ENSP00000441992

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21262 AN: 152148 Hom.: 1568 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0503

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.139 AC: 59879 AN: 431690 Hom.: 4749 Cov.: 5 AF XY: 0.143 AC XY: 32722 AN XY: 228184

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0847

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.0470

Gnomad4 SAS exome AF: 0.224

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.135

GnomAD4 genome AF: 0.140 AC: 21267 AN: 152266 Hom.: 1567 Cov.: 33 AF XY: 0.140 AC XY: 10441 AN XY: 74462

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0974

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0499

Gnomad4 SAS AF: 0.233

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.134

Alfa AF: 0.139 Hom.: 339

Bravo AF: 0.132

Asia WGS AF: 0.150 AC: 523 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	-0.90
CADD	Benign	2.4
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17482467; hg19: chr1-167778705;