rs34303217
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1BS2_Supporting
The NM_000681.4(ADRA2A):c.*130T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 988,308 control chromosomes in the GnomAD database, including 18 homozygotes. 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 0.0075 ( 10 hom., cov: 33)
Exomes 𝑓: 0.00074 ( 8 hom. )
Consequence
ADRA2A
NM_000681.4 3_prime_UTR
NM_000681.4 3_prime_UTR
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -2.38
Genes affected
ADRA2A (HGNC:281): (adrenoceptor alpha 2A) Alpha-2-adrenergic receptors are members of the G protein-coupled receptor superfamily. The alpha-2-adrenergic receptors are a type of adrenergic receptors (for adrenaline or epinephrine), which inhibit adenylate cyclase. These receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. They are involved in regulating the release of neurotransmitter molecules from sympathetic nerves and from adrenergic neurons in the central nervous system. The sympathetic nervous system regulates cardiovascular function by activating adrenergic receptors in the heart, blood vessels and kidney. Studies in mouse revealed that both the alpha2A and alpha2C receptor subtypes were required for presynaptic transmitter release from the sympathetic nervous system in the heart and from central noradrenergic neurons. The alpha-2-adrenergic receptors are also involved in catecholamine signaling by extracellular regulated protein kinase 1 and 2 (ERK1/2) pathways. A clear association between the alpha-2-adrenergic receptor and disease has not been yet established. [provided by RefSeq, Sep 2019]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00751 (1144/152342) while in subpopulation AFR AF= 0.0261 (1084/41580). AF 95% confidence interval is 0.0248. There are 10 homozygotes in gnomad4. There are 561 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 10 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADRA2A | NM_000681.4 | c.*130T>A | 3_prime_UTR_variant | 1/1 | ENST00000280155.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADRA2A | ENST00000280155.4 | c.*130T>A | 3_prime_UTR_variant | 1/1 | NM_000681.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00746 AC: 1135AN: 152224Hom.: 10 Cov.: 33
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GnomAD4 exome AF: 0.000736 AC: 615AN: 835966Hom.: 8 Cov.: 11 AF XY: 0.000714 AC XY: 302AN XY: 423170
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GnomAD4 genome ? AF: 0.00751 AC: 1144AN: 152342Hom.: 10 Cov.: 33 AF XY: 0.00753 AC XY: 561AN XY: 74496
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ClinVar
Not reported inComputational scores
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Name
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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