Variant 7-45574801-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_021116.4(ADCY1):c.258C>G(p.Pro86Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,571,524 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 10 hom. )

Consequence

ADCY1
NM_021116.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.149

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 7-45574801-C-G is Benign according to our data. Variant chr7-45574801-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-45574801-C-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.149 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADCY1	NM_021116.4 link	c.258C>G	p.Pro86Pro	synonymous_variant	1/20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4 link	c.258C>G	p.Pro86Pro	synonymous_variant	1/19		XP_005249641.1
ADCY1	XM_005249585.3 link	c.258C>G	p.Pro86Pro	synonymous_variant	1/9		XP_005249642.1
ADCY1	NM_001281768.2 link	c.-330-88C>G		intron_variant			NP_001268697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12 link	c.258C>G	p.Pro86Pro	synonymous_variant	1/20	1	NM_021116.4	ENSP00000297323.7		Q08828
ADCY1	ENST00000432715.5 link	c.-330-88C>G		intron_variant		2		ENSP00000392721.1		C9J1J0

Frequencies

GnomAD3 genomes

AF:

0.000687

AC:

104

AN:

151470

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.000869

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.000724

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.00152

AC:

285

AN:

187354

Hom.:

AF XY:

0.00181

AC XY:

191

AN XY:

105400

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000380

Gnomad ASJ exome

AF:

0.00183

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00743

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000688

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.000842

AC:

1196

AN:

1419948

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

747

AN XY:

705336

show subpopulations

Gnomad4 AFR exome

AF:

0.000306

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00177

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00675

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.000415

Gnomad4 OTH exome

AF:

0.00125

GnomAD4 genome

AF:

0.000686

AC:

104

AN:

151576

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

AN XY:

74066

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.000869

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000724

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.00110

Hom.:

Bravo

AF:

0.000706

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 27, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2025	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.73

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