5-159972140-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_000679.4(ADRA1B):āc.1211A>Gā(p.Lys404Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000089 in 1,348,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 29)
Exomes š: 0.0000092 ( 0 hom. )
Consequence
ADRA1B
NM_000679.4 missense
NM_000679.4 missense
Scores
2
2
15
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 3.97
Genes affected
ADRA1B (HGNC:278): (adrenoceptor alpha 1B) Alpha-1-adrenergic receptors (alpha-1-ARs) are members of the G protein-coupled receptor superfamily. They activate mitogenic responses and regulate growth and proliferation of many cells. There are 3 alpha-1-AR subtypes: alpha-1A, -1B and -1D, all of which signal through the Gq/11 family of G-proteins and different subtypes show different patterns of activation. This gene encodes alpha-1B-adrenergic receptor, which induces neoplastic transformation when transfected into NIH 3T3 fibroblasts and other cell lines. Thus, this normal cellular gene is identified as a protooncogene. This gene comprises 2 exons and a single large intron of at least 20 kb that interrupts the coding region. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22268546).
BS2
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADRA1B | NM_000679.4 | c.1211A>G | p.Lys404Arg | missense_variant | 2/2 | ENST00000306675.5 | |
ADRA1B | XM_011534435.2 | c.1319A>G | p.Lys440Arg | missense_variant | 5/5 | ||
ADRA1B | XM_047416776.1 | c.1319A>G | p.Lys440Arg | missense_variant | 6/6 | ||
ADRA1B | XM_006714821.4 | c.950-13531A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADRA1B | ENST00000306675.5 | c.1211A>G | p.Lys404Arg | missense_variant | 2/2 | 1 | NM_000679.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000664 AC: 1AN: 150706Hom.: 0 Cov.: 29
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GnomAD4 exome AF: 0.00000918 AC: 11AN: 1197806Hom.: 0 Cov.: 44 AF XY: 0.00000855 AC XY: 5AN XY: 584606
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GnomAD4 genome AF: 0.00000664 AC: 1AN: 150706Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 73540
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of ubiquitination at K404 (P = 8e-04);
MVP
MPC
ClinPred
D
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at