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GeneBe

16-3966354-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001116.4(ADCY9):c.3483C>T(p.Phe1161=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00209 in 1,614,108 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 26 hom., cov: 33)
Exomes 𝑓: 0.0011 ( 31 hom. )

Consequence

ADCY9
NM_001116.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.713
Variant links:
Genes affected
ADCY9 (HGNC:240): (adenylate cyclase 9) Adenylate cyclase is a membrane bound enzyme that catalyses the formation of cyclic AMP from ATP. It is regulated by a family of G protein-coupled receptors, protein kinases, and calcium. The type 9 adenylyl cyclase is a widely distributed adenylyl cyclase, and it is stimulated by beta-adrenergic receptor activation but is insensitive to forskolin, calcium, and somatostatin. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-3966354-G-A is Benign according to our data. Variant chr16-3966354-G-A is described in ClinVar as [Benign]. Clinvar id is 768749.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.713 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0116 (1764/152296) while in subpopulation AFR AF= 0.0405 (1684/41550). AF 95% confidence interval is 0.0389. There are 26 homozygotes in gnomad4. There are 814 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1758 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADCY9NM_001116.4 linkuse as main transcriptc.3483C>T p.Phe1161= synonymous_variant 11/11 ENST00000294016.8
ADCY9XM_005255079.4 linkuse as main transcriptc.3540C>T p.Phe1180= synonymous_variant 11/11
ADCY9XM_011522353.3 linkuse as main transcriptc.2927+8315C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADCY9ENST00000294016.8 linkuse as main transcriptc.3483C>T p.Phe1161= synonymous_variant 11/111 NM_001116.4 P1
ADCY9ENST00000576936.5 linkuse as main transcriptc.567+8315C>T intron_variant 5

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0116
AC:
1758
AN:
152178
Hom.:
26
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0405
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00347
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00958
GnomAD3 exomes
AF:
0.00305
AC:
764
AN:
250718
Hom.:
10
AF XY:
0.00224
AC XY:
303
AN XY:
135546
show subpopulations
Gnomad AFR exome
AF:
0.0410
Gnomad AMR exome
AF:
0.00237
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000972
Gnomad OTH exome
AF:
0.000978
GnomAD4 exome
AF:
0.00110
AC:
1606
AN:
1461812
Hom.:
31
Cov.:
33
AF XY:
0.000913
AC XY:
664
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.0399
Gnomad4 AMR exome
AF:
0.00237
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000324
Gnomad4 OTH exome
AF:
0.00209
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0116
AC:
1764
AN:
152296
Hom.:
26
Cov.:
33
AF XY:
0.0109
AC XY:
814
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.0405
Gnomad4 AMR
AF:
0.00346
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00948
Alfa
AF:
0.00565
Hom.:
15
Bravo
AF:
0.0129
Asia WGS
AF:
0.00231
AC:
8
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.51
Cadd
Benign
5.7
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.

Other links and lift over

dbSNP: rs74003478; hg19: chr16-4016355; API