rs760606743
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_021116.4(ADCY1):c.100C>A(p.Arg34Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000794 in 1,260,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000081 ( 0 hom. )
Consequence
ADCY1
NM_021116.4 synonymous
NM_021116.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.73
Publications
1 publications found
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 Gene-Disease associations (from GenCC):
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
- nonsyndromic genetic hearing lossInheritance: AR Classification: LIMITED Submitted by: ClinGen
- autosomal recessive nonsyndromic hearing loss 44Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.67).
BP7
Synonymous conserved (PhyloP=1.73 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_021116.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ADCY1 | NM_021116.4 | MANE Select | c.100C>A | p.Arg34Arg | synonymous | Exon 1 of 20 | NP_066939.1 | Q08828 | |
| ADCY1 | NM_001281768.2 | c.-330-246C>A | intron | N/A | NP_001268697.1 | C9J1J0 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| ADCY1 | ENST00000297323.12 | TSL:1 MANE Select | c.100C>A | p.Arg34Arg | synonymous | Exon 1 of 20 | ENSP00000297323.7 | Q08828 | |
| ADCY1 | ENST00000920696.1 | c.100C>A | p.Arg34Arg | synonymous | Exon 1 of 19 | ENSP00000590755.1 | |||
| ADCY1 | ENST00000432715.5 | TSL:2 | c.-330-246C>A | intron | N/A | ENSP00000392721.1 | C9J1J0 |
Frequencies
GnomAD3 genomes 0.00000670 AC: 1AN: 149326Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
149326
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000810 AC: 9AN: 1110898Hom.: 0 Cov.: 30 AF XY: 0.0000113 AC XY: 6AN XY: 532032 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1110898
Hom.:
Cov.:
30
AF XY:
AC XY:
6
AN XY:
532032
show subpopulations
African (AFR)
AF:
AC:
0
AN:
22264
American (AMR)
AF:
AC:
0
AN:
8608
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
14384
East Asian (EAS)
AF:
AC:
0
AN:
24388
South Asian (SAS)
AF:
AC:
0
AN:
32256
European-Finnish (FIN)
AF:
AC:
0
AN:
24778
Middle Eastern (MID)
AF:
AC:
0
AN:
2960
European-Non Finnish (NFE)
AF:
AC:
9
AN:
937144
Other (OTH)
AF:
AC:
0
AN:
44116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.453
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
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10
<30
30-35
35-40
40-45
45-50
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55-60
60-65
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>80
Age
GnomAD4 genome 0.00000670 AC: 1AN: 149326Hom.: 0 Cov.: 32 AF XY: 0.0000137 AC XY: 1AN XY: 72826 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
149326
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
72826
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41060
American (AMR)
AF:
AC:
0
AN:
15014
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3446
East Asian (EAS)
AF:
AC:
0
AN:
5084
South Asian (SAS)
AF:
AC:
0
AN:
4818
European-Finnish (FIN)
AF:
AC:
0
AN:
9456
Middle Eastern (MID)
AF:
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67166
Other (OTH)
AF:
AC:
0
AN:
2058
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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