Variant rs2293106 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021116.4(ADCY1):c.3090G>A(p.Arg1030Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 780,528 control chromosomes in the GnomAD database, including 11,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3429 hom., cov: 33)

Exomes 𝑓: 0.15 ( 7776 hom. )

Consequence

ADCY1
NM_021116.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

ADCY1 (HGNC:232): (adenylate cyclase 1) This gene encodes a member of the of adenylate cyclase gene family that is primarily expressed in the brain. This protein is regulated by calcium/calmodulin concentration and may be involved in brain development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ADCY1 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=-0.75).

BP6

Variant 7-45713725-G-A is Benign according to our data. Variant chr7-45713725-G-A is described in ClinVar as [Benign]. Clinvar id is 517532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADCY1	NM_021116.4 link	c.3090G>A	p.Arg1030Arg	synonymous_variant	Exon 20 of 20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4 link	c.*25G>A		3_prime_UTR_variant	Exon 19 of 19		XP_005249641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12 link	c.3090G>A	p.Arg1030Arg	synonymous_variant	Exon 20 of 20	1	NM_021116.4	ENSP00000297323.7		Q08828

Frequencies

GnomAD3 genomes

AF:

0.197

AC:

29976

AN:

152158

Hom.:

3425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.227

Gnomad AMR

AF:

0.141

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.0434

Gnomad FIN

AF:

0.134

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.209

GnomAD3 exomes

AF:

0.147

AC:

36842

AN:

251350

Hom.:

3315

AF XY:

0.142

AC XY:

19331

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.0990

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.110

Gnomad SAS exome

AF:

0.0451

Gnomad FIN exome

AF:

0.130

Gnomad NFE exome

AF:

0.168

Gnomad OTH exome

AF:

0.159

GnomAD4 exome

AF:

0.145

AC:

91302

AN:

628252

Hom.:

7776

Cov.:

AF XY:

0.140

AC XY:

48050

AN XY:

342276

show subpopulations

Gnomad4 AFR exome

AF:

0.316

Gnomad4 AMR exome

AF:

0.105

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.0777

Gnomad4 SAS exome

AF:

0.0444

Gnomad4 FIN exome

AF:

0.129

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.164

GnomAD4 genome

AF:

0.197

AC:

29989

AN:

152276

Hom.:

3429

Cov.:

AF XY:

0.192

AC XY:

14318

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.315

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.200

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.0424

Gnomad4 FIN

AF:

0.134

Gnomad4 NFE

AF:

0.164

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.185

Hom.:

1262

Bravo

AF:

0.208

Asia WGS

AF:

0.0900

AC:

319

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.183

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 03, 2025	- -

Autosomal recessive nonsyndromic hearing loss 44

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.Arg1030Arg in exon 20 of ADCY1: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 31.47% (3265/10374 ) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs2293106). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.2

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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