rs1801253

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000684.3(ADRB1):​c.1165G>A​(p.Gly389Arg) 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. 12/18 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 nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G389V) has been classified as Benign.

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ADRB1
NM_000684.3 missense

Scores

1
1
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04
Variant links:
Genes affected
ADRB1 (HGNC:285): (adrenoceptor beta 1) The adrenergic receptors (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. Beta-1 adrenoceptors are predominately located in the heart. Specific polymorphisms in this gene have been shown to affect the resting heart rate and can be involved in heart failure. [provided by RefSeq, Sep 2019]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.059390485).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADRB1NM_000684.3 linkuse as main transcriptc.1165G>A p.Gly389Arg missense_variant 1/1 ENST00000369295.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADRB1ENST00000369295.4 linkuse as main transcriptc.1165G>A p.Gly389Arg missense_variant 1/1 NM_000684.3 P1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1427478
Hom.:
0
Cov.:
58
AF XY:
0.00
AC XY:
0
AN XY:
710218
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
15
DANN
Benign
0.96
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.28
N
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.059
T
MetaSVM
Benign
-0.97
T
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.89
D
PROVEAN
Benign
3.2
N
REVEL
Benign
0.071
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Vest4
0.055
MutPred
0.32
Gain of MoRF binding (P = 0.02);
MVP
0.51
ClinPred
0.48
T
GERP RS
1.7
gMVP
0.54

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: rs1801253; hg19: chr10-115805056; API