rs1034463

Positions:

• chr1-167837409-T-A
• chr1-167837409-T-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.3008-91A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.666 in 1,203,410 control chromosomes in the GnomAD database, including 269,541 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40942 hom., cov: 32)
  • Exomes 𝑓: 0.66 (228599 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.718

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=-0.92).
• BP6: Variant 1-167837409-T-A is Benign according to our data. Variant chr1-167837409-T-A is described in ClinVar as [Benign]. Clinvar id is 1253001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.3008-91A>T		intron_variant		ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.3008-91A>T		intron_variant		1	NM_018417.6	ENSP00000356825	P1
ADCY10	ENST00000367848.1	c.2732-91A>T		intron_variant		1		ENSP00000356822
ADCY10	ENST00000545172.5	c.2549-91A>T		intron_variant		2		ENSP00000441992
ADCY10	ENST00000485964.5	c.700-2715A>T		intron_variant, NMD_transcript_variant		5		ENSP00000476402

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109938 AN: 152048 Hom.: 40875 Cov.: 32

Gnomad AFR AF: 0.904

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.657 AC: 691140 AN: 1051244 Hom.: 228599 AF XY: 0.653 AC XY: 351216 AN XY: 537522

Gnomad4 AFR exome AF: 0.912

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.552

Gnomad4 SAS exome AF: 0.594

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.655

Gnomad4 OTH exome AF: 0.662

GnomAD4 genome AF: 0.723 AC: 110065 AN: 152166 Hom.: 40942 Cov.: 32 AF XY: 0.718 AC XY: 53394 AN XY: 74368

Gnomad4 AFR AF: 0.904

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.512

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.702

Alfa AF: 0.690 Hom.: 4661

Bravo AF: 0.740

Asia WGS AF: 0.595 AC: 2070 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	-0.92
CADD	Benign	0.56
DANN	Benign	0.55

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: rs1034463; hg19: chr1-167806647; COSMIC: COSV63239231;