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GeneBe

rs1042714

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000024.6(ADRB2):c.79G>A(p.Glu27Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E27Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Consequence

ADRB2
NM_000024.6 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44
Variant links:
Genes affected
ADRB2 (HGNC:286): (adrenoceptor beta 2) This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson's Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease. [provided by RefSeq, Oct 2019]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10279137).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADRB2NM_000024.6 linkuse as main transcriptc.79G>A p.Glu27Lys missense_variant 1/1 ENST00000305988.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADRB2ENST00000305988.6 linkuse as main transcriptc.79G>A p.Glu27Lys missense_variant 1/1 NM_000024.6 P1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
67
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.41
Cadd
Benign
18
Dann
Uncertain
0.99
DEOGEN2
Benign
0.11
T
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.86
D
M_CAP
Benign
0.0068
T
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.55
T
PROVEAN
Benign
-0.29
N
REVEL
Benign
0.10
Sift
Benign
0.39
T
Sift4G
Benign
0.79
T
Polyphen
0.0090
B
Vest4
0.14
MutPred
0.52
Gain of methylation at E27 (P = 0.0047);
MVP
0.43
MPC
0.59
ClinPred
0.17
T
GERP RS
4.0
Varity_R
0.068
gMVP
0.45

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: rs1042714; hg19: chr5-148206473; API