1-167809759-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018417.6(ADCY10):c.4752T>C(p.Ile1584=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,614,126 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0072 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (17 hom.)
• Consequence: ADCY10 NM_018417.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.582

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-167809759-A-G is Benign according to our data. Variant chr1-167809759-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 720996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.582 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00721 (1098/152300) while in subpopulation AFR AF= 0.0247 (1026/41546). AF 95% confidence interval is 0.0234. There are 8 homozygotes in gnomad4. There are 552 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1085 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6	c.4752T>C	p.Ile1584=	synonymous_variant	33/33	ENST00000367851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY10	ENST00000367851.9	c.4752T>C	p.Ile1584=	synonymous_variant	33/33	1	NM_018417.6	P1
ADCY10	ENST00000367848.1	c.4476T>C	p.Ile1492=	synonymous_variant	33/33	1
ADCY10	ENST00000545172.5	c.4293T>C	p.Ile1431=	synonymous_variant	30/30	2
ADCY10	ENST00000485964.5	c.*1688T>C		3_prime_UTR_variant, NMD_transcript_variant	15/15	5

Frequencies

GnomAD3 genomes AF: 0.00713 AC: 1085 AN: 152182 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00192 AC: 484 AN: 251442 Hom.: 9 AF XY: 0.00145 AC XY: 197 AN XY: 135896

Gnomad AFR exome AF: 0.0266

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000767 AC: 1121 AN: 1461826 Hom.: 17 Cov.: 31 AF XY: 0.000652 AC XY: 474 AN XY: 727218

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000162

Gnomad4 OTH exome AF: 0.00166

GnomAD4 genome AF: 0.00721 AC: 1098 AN: 152300 Hom.: 8 Cov.: 32 AF XY: 0.00741 AC XY: 552 AN XY: 74490

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00264 Hom.: 3

Bravo AF: 0.00796

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Familial idiopathic hypercalciuria Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.13
Dann	Benign	0.51

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: rs59725214; hg19: chr1-167778996;