Variant 7-45574599-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021116.4(ADCY1):c.56G>A(p.Gly19Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000452 in 1,106,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000010 ( 0 hom. )

Consequence

ADCY1
NM_021116.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.805

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19005844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADCY1	NM_021116.4 link	c.56G>A	p.Gly19Glu	missense_variant	1/20	ENST00000297323.12	NP_066939.1
ADCY1	XM_005249584.4 link	c.56G>A	p.Gly19Glu	missense_variant	1/19		XP_005249641.1
ADCY1	XM_005249585.3 link	c.56G>A	p.Gly19Glu	missense_variant	1/9		XP_005249642.1
ADCY1	NM_001281768.2 link	c.-330-290G>A		intron_variant			NP_001268697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADCY1	ENST00000297323.12 link	c.56G>A	p.Gly19Glu	missense_variant	1/20	1	NM_021116.4	ENSP00000297323.7		Q08828
ADCY1	ENST00000432715.5 link	c.-330-290G>A		intron_variant		2		ENSP00000392721.1		C9J1J0

Frequencies

GnomAD3 genomes

AF:

0.0000274

AC:

AN:

145952

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:

0.000201

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000456

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000104

AC:

AN:

960834

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

451076

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000274

AC:

AN:

146040

Hom.:

Cov.:

AF XY:

0.0000422

AC XY:

AN XY:

71104

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000202

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000456

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.23

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.40

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.40

REVEL

Benign

0.18

Sift

Benign

0.14

Sift4G

Benign

0.084

Polyphen

0.18

Vest4

0.20

MutPred

0.16

Loss of loop (P = 0.0203);

MVP

0.58

MPC

1.6

ClinPred

0.22

GERP RS

1.9

Varity_R

0.082

gMVP

0.19

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over