7-45574791-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2

The NM_021116.4(ADCY1):c.248C>T(p.Ala83Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,546,094 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 8 hom. )

Consequence

ADCY1
NM_021116.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.678

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.

PP2

Missense variant where missense usually causes diseases, ADCY1

BP4

Computational evidence support a benign effect (MetaRNN=0.007783115).

BP6

Variant 7-45574791-C-T is Benign according to our data. Variant chr7-45574791-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADCY1	NM_021116.4 linkuse as main transcript	c.248C>T	p.Ala83Val	missense_variant	1/20	ENST00000297323.12
ADCY1	XM_005249584.4 linkuse as main transcript	c.248C>T	p.Ala83Val	missense_variant	1/19
ADCY1	XM_005249585.3 linkuse as main transcript	c.248C>T	p.Ala83Val	missense_variant	1/9
ADCY1	NM_001281768.2 linkuse as main transcript	c.-330-98C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADCY1	ENST00000297323.12 linkuse as main transcript	c.248C>T	p.Ala83Val	missense_variant	1/20	1	NM_021116.4	P1
ADCY1	ENST00000432715.5 linkuse as main transcript	c.-330-98C>T		intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000238

AC:

AN:

150948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00731

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.00145

AC:

221

AN:

152788

Hom.:

AF XY:

0.00201

AC XY:

173

AN XY:

86036

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00965

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000516

GnomAD4 exome

AF:

0.000520

AC:

725

AN:

1395046

Hom.:

Cov.:

AF XY:

0.000784

AC XY:

542

AN XY:

691058

show subpopulations

Gnomad4 AFR exome

AF:

0.0000692

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00875

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.000486

GnomAD4 genome

AF:

0.000238

AC:

AN:

151048

Hom.:

Cov.:

AF XY:

0.000406

AC XY:

AN XY:

73814

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00731

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.0000921

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.00126

AC:

145

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jul 25, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.25

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0078

MetaSVM

Benign

-0.80

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.1

REVEL

Benign

0.21

Sift

Benign

0.32

Sift4G

Benign

0.24

Polyphen

0.71

Vest4

0.20

MutPred

0.56

Loss of disorder (P = 0.0508);

MVP

0.83

MPC

1.3

ClinPred

0.043

GERP RS

0.51

Varity_R

0.042

gMVP

0.28

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