chr1-167810628-A-C

Position:

• chr1-167810628-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.4671+97T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0803 in 1,141,038 control chromosomes in the GnomAD database, including 4,170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (424 hom., cov: 32)
  • Exomes 𝑓: 0.082 (3746 hom.)
• Consequence: ADCY10 NM_018417.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.164

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=-0.85).
• BP6: Variant 1-167810628-A-C is Benign according to our data. Variant chr1-167810628-A-C is described in ClinVar as [Benign]. Clinvar id is 1248268.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADCY10	NM_018417.6	c.4671+97T>G		intron_variant		ENST00000367851.9	NP_060887.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY10	ENST00000367851.9	c.4671+97T>G		intron_variant		1	NM_018417.6	ENSP00000356825	P1
ADCY10	ENST00000367848.1	c.4395+97T>G		intron_variant		1		ENSP00000356822
ADCY10	ENST00000545172.5	c.4212+97T>G		intron_variant		2		ENSP00000441992
ADCY10	ENST00000485964.5	c.*1607+97T>G		intron_variant, NMD_transcript_variant		5		ENSP00000476402

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10871 AN: 152106 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0535

Gnomad ASJ AF: 0.102

Gnomad EAS AF: 0.0428

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0730

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0822

GnomAD4 exome AF: 0.0817 AC: 80780 AN: 988814 Hom.: 3746 AF XY: 0.0846 AC XY: 42928 AN XY: 507636

Gnomad4 AFR exome AF: 0.0571

Gnomad4 AMR exome AF: 0.0427

Gnomad4 ASJ exome AF: 0.0948

Gnomad4 EAS exome AF: 0.0439

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0758

Gnomad4 NFE exome AF: 0.0804

Gnomad4 OTH exome AF: 0.0818

GnomAD4 genome AF: 0.0714 AC: 10867 AN: 152224 Hom.: 424 Cov.: 32 AF XY: 0.0710 AC XY: 5281 AN XY: 74426

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.102

Gnomad4 EAS AF: 0.0425

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0730

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.0814

Alfa AF: 0.0697 Hom.: 48

Bravo AF: 0.0693

Asia WGS AF: 0.0850 AC: 297 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	-0.85
CADD	Benign	4.1
DANN	Benign	0.72

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: rs74486783; hg19: chr1-167779865; COSMIC: COSV63242383;