rs78087585

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_021116.4(ADCY1):c.897C>T(p.His299=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00391 in 1,613,608 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 28 hom. )

Consequence

ADCY1
NM_021116.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.163

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 7-45610486-C-T is Benign according to our data. Variant chr7-45610486-C-T is described in ClinVar as [Benign]. Clinvar id is 517530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-45610486-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.163 with no splicing effect.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADCY1	NM_021116.4 linkuse as main transcript	c.897C>T	p.His299=	synonymous_variant	3/20	ENST00000297323.12
ADCY1	NM_001281768.2 linkuse as main transcript	c.222C>T	p.His74=	synonymous_variant	4/10
ADCY1	XM_005249584.4 linkuse as main transcript	c.897C>T	p.His299=	synonymous_variant	3/19
ADCY1	XM_005249585.3 linkuse as main transcript	c.897C>T	p.His299=	synonymous_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ADCY1	ENST00000297323.12 linkuse as main transcript	c.897C>T	p.His299=	synonymous_variant	3/20	1	NM_021116.4	P1
ADCY1	ENST00000432715.5 linkuse as main transcript	c.222C>T	p.His74=	synonymous_variant	4/10	2
ADCY1	ENST00000621543.1 linkuse as main transcript	c.222C>T	p.His74=	synonymous_variant	3/9	5

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

655

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00633

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00504

Gnomad ASJ

AF:

0.00952

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.000849

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00356

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00321

AC:

800

AN:

249252

Hom.:

AF XY:

0.00332

AC XY:

448

AN XY:

134928

show subpopulations

Gnomad AFR exome

AF:

0.00621

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.0101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00212

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.00507

GnomAD4 exome

AF:

0.00387

AC:

5655

AN:

1461432

Hom.:

Cov.:

AF XY:

0.00390

AC XY:

2838

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.00601

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00279

Gnomad4 FIN exome

AF:

0.00152

Gnomad4 NFE exome

AF:

0.00386

Gnomad4 OTH exome

AF:

0.00586

GnomAD4 genome

AF:

0.00433

AC:

659

AN:

152176

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.00641

Gnomad4 AMR

AF:

0.00504

Gnomad4 ASJ

AF:

0.00952

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.000849

Gnomad4 NFE

AF:

0.00356

Gnomad4 OTH

AF:

0.00615

Alfa

AF:

0.00473

Hom.:

Bravo

AF:

0.00494

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00474

EpiControl

AF:

0.00391

ClinVar

Significance: 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	clinical testing	GeneDx	Feb 15, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 16, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 23, 2017

p.His299His in exon 3 of ADCY1: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.62% (64/10396) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs78087585). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

Cadd

Benign

3.6

Dann

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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