Variant 1-167809759-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.582

Variant links:

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]

ADCY10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 1098 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADCY10	NM_018417.6 linkuse as main transcript	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 linkuse as main transcript	c.4752T>C	p.Ile1584=	synonymous_variant	33/33	1	NM_018417.6	P1	Q96PN6-1
ADCY10	ENST00000367848.1 linkuse as main transcript	c.4476T>C	p.Ile1492=	synonymous_variant	33/33	1			Q96PN6-2
ADCY10	ENST00000545172.5 linkuse as main transcript	c.4293T>C	p.Ile1431=	synonymous_variant	30/30	2			Q96PN6-4
ADCY10	ENST00000485964.5 linkuse as main transcript	c.*1688T>C		3_prime_UTR_variant, NMD_transcript_variant	15/15	5

Frequencies

GnomAD3 genomes

AF:

0.00713

AC:

1085

AN:

152182

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00145

AC XY:

197

AN XY:

135896

show subpopulations

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.:

Cov.:

AF XY:

0.000652

AC XY:

474

AN XY:

727218

show subpopulations

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.:

Cov.:

AF XY:

0.00741

AC XY:

552

AN XY:

74490

show subpopulations

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.:

Bravo

AF:

0.00796

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over