NM_021116.4:c.1554C>T

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_021116.4(ADCY1):c.1554C>T(p.Phe518Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.0208 in 1,613,988 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 31 hom., cov: 32)

Exomes 𝑓: 0.021 ( 413 hom. )

Consequence

ADCY1
NM_021116.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.70

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 7-45662163-C-T is Benign according to our data. Variant chr7-45662163-C-T is described in ClinVar as [Benign]. Clinvar id is 517531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0155 (2359/152284) while in subpopulation NFE AF= 0.0241 (1640/68030). AF 95% confidence interval is 0.0231. There are 31 homozygotes in gnomad4. There are 1190 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ADCY1	NM_021116.4 link	c.1554C>T	p.Phe518Phe	synonymous_variant	Exon 8 of 20	ENST00000297323.12	NP_066939.1
ADCY1	NM_001281768.2 link	c.879C>T	p.Phe293Phe	synonymous_variant	Exon 9 of 10		NP_001268697.1
ADCY1	XM_005249584.4 link	c.1554C>T	p.Phe518Phe	synonymous_variant	Exon 8 of 19		XP_005249641.1
ADCY1	XM_005249585.3 link	c.1554C>T	p.Phe518Phe	synonymous_variant	Exon 8 of 9		XP_005249642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADCY1	ENST00000297323.12 link	c.1554C>T	p.Phe518Phe	synonymous_variant	Exon 8 of 20	1	NM_021116.4	ENSP00000297323.7	Q08828
ADCY1	ENST00000432715.5 link	c.879C>T	p.Phe293Phe	synonymous_variant	Exon 9 of 10	2		ENSP00000392721.1	C9J1J0
ADCY1	ENST00000621543.1 link	c.879C>T	p.Phe293Phe	synonymous_variant	Exon 8 of 9	5		ENSP00000479770.1	C9J1J0
ADCY1	ENST00000646653.1 link	n.495C>T		non_coding_transcript_exon_variant	Exon 4 of 8

Frequencies

GnomAD3 genomes

AF:

0.0155

AC:

2362

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00700

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0237

Gnomad FIN

AF:

0.0271

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0241

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0180

AC:

4523

AN:

251098

Hom.:

AF XY:

0.0192

AC XY:

2607

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00437

Gnomad AMR exome

AF:

0.00695

Gnomad ASJ exome

AF:

0.00904

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0254

Gnomad FIN exome

AF:

0.0266

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0213

AC:

31207

AN:

1461704

Hom.:

413

Cov.:

AF XY:

0.0217

AC XY:

15807

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.00343

Gnomad4 AMR exome

AF:

0.00722

Gnomad4 ASJ exome

AF:

0.00899

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0263

Gnomad4 FIN exome

AF:

0.0269

Gnomad4 NFE exome

AF:

0.0230

Gnomad4 OTH exome

AF:

0.0187

GnomAD4 genome

AF:

0.0155

AC:

2359

AN:

152284

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1190

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00296

Gnomad4 AMR

AF:

0.00699

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0230

Gnomad4 FIN

AF:

0.0271

Gnomad4 NFE

AF:

0.0241

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0196

Hom.:

Bravo

AF:

0.0130

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0243

EpiControl

AF:

0.0222

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 31, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Phe518Phe in exon 8 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 2.67% (420/15720) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs61729596). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.80

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