chr1-167846372-C-A

Position:

• chr1-167846372-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018417.6(ADCY10):​c.2438-109G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,383,640 control chromosomes in the GnomAD database, including 87,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7955 hom., cov: 32)
  • Exomes 𝑓: 0.36 (79389 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-167846372-C-A is Benign according to our data. Variant chr1-167846372-C-A is described in ClinVar as [Benign]. Clinvar id is 1183578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.2438-109G>T		intron_variant		ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.2438-109G>T		intron_variant		1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.2162-109G>T		intron_variant		1
ADCY10	ENST00000545172.5	c.1979-109G>T		intron_variant		2
ADCY10	ENST00000485964.5	c.130-109G>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48277 AN: 151944 Hom.: 7951 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.357 AC: 439224 AN: 1231578 Hom.: 79389 AF XY: 0.353 AC XY: 219544 AN XY: 621928

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.363

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.253

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.368

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.318 AC: 48289 AN: 152062 Hom.: 7955 Cov.: 32 AF XY: 0.315 AC XY: 23379 AN XY: 74312

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.318

Alfa AF: 0.341 Hom.: 4050

Bravo AF: 0.314

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	0.36
DANN	Benign	0.34

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: rs2269679; hg19: chr1-167815610; COSMIC: COSV63241697;