7-45686021-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_021116.4(ADCY1):c.2133G>A(p.Ser711=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 0 hom. )
Consequence
ADCY1
NM_021116.4 synonymous
NM_021116.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.59
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 7-45686021-G-A is Benign according to our data. Variant chr7-45686021-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 517562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.59 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADCY1 | NM_021116.4 | c.2133G>A | p.Ser711= | synonymous_variant | 13/20 | ENST00000297323.12 | |
ADCY1 | XM_005249584.4 | c.2133G>A | p.Ser711= | synonymous_variant | 13/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY1 | ENST00000297323.12 | c.2133G>A | p.Ser711= | synonymous_variant | 13/20 | 1 | NM_021116.4 | P1 | |
ADCY1 | ENST00000468353.1 | n.744G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152100Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000559 AC: 14AN: 250426Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135418
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GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461788Hom.: 0 Cov.: 33 AF XY: 0.0000413 AC XY: 30AN XY: 727206
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74422
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2017 | p.Ser711Ser in exon 13 of ADCY1: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.03% (3/10346) o f African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs149908239). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 01, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at