NM_000684.3:c.1165G>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000684.3(ADRB1):c.1165G>C(p.Gly389Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 1,577,268 control chromosomes in the GnomAD database, including 423,077 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G389V) has been classified as Benign.

Frequency

Genomes: 𝑓 0.70 ( 36948 hom., cov: 34)

Exomes 𝑓: 0.73 ( 386129 hom. )

Consequence

ADRB1
NM_000684.3 missense

Scores

Clinical Significance

Benign; association no assertion criteria provided B:2O:1

Conservation

PhyloP100: 1.04

Publications

603 publications found

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]

ADRB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.993127E-7).

BP6

Variant 10-114045297-G-C is Benign according to our data. Variant chr10-114045297-G-C is described in ClinVar as Benign|association. ClinVar VariationId is 17746.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000684.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB1	NM_000684.3	MANE Select	c.1165G>C	p.Gly389Arg	missense	Exon 1 of 1	NP_000675.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB1	ENST00000369295.4	TSL:6 MANE Select	c.1165G>C	p.Gly389Arg	missense	Exon 1 of 1	ENSP00000358301.2

Frequencies

GnomAD3 genomes

AF:

0.696

AC:

104769

AN:

150514

Hom.:

36905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.616

Gnomad AMR

AF:

0.776

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.763

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.743

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.732

Gnomad OTH

AF:

0.681

GnomAD2 exomes

AF:

0.737

AC:

162149

AN:

219864

AF XY:

0.735

show subpopulations

Gnomad AFR exome

AF:

0.578

Gnomad AMR exome

AF:

0.859

Gnomad ASJ exome

AF:

0.625

Gnomad EAS exome

AF:

0.745

Gnomad FIN exome

AF:

0.739

Gnomad NFE exome

AF:

0.725

Gnomad OTH exome

AF:

0.717

GnomAD4 exome

AF:

0.734

AC:

1047689

AN:

1426646

Hom.:

386129

Cov.:

AF XY:

0.735

AC XY:

521652

AN XY:

709768

show subpopulations

African (AFR)

AF:

0.579

AC:

18120

AN:

31314

American (AMR)

AF:

0.846

AC:

35078

AN:

41450

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

15648

AN:

25222

East Asian (EAS)

AF:

0.781

AC:

28390

AN:

36338

South Asian (SAS)

AF:

0.755

AC:

62671

AN:

82964

European-Finnish (FIN)

AF:

0.746

AC:

38391

AN:

51444

Middle Eastern (MID)

AF:

0.614

AC:

3476

AN:

5664

European-Non Finnish (NFE)

AF:

0.735

AC:

803713

AN:

1093620

Other (OTH)

AF:

0.720

AC:

42202

AN:

58630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

15000

30000

45001

60001

75001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19958

39916

59874

79832

99790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.696

AC:

104861

AN:

150622

Hom.:

36948

Cov.:

AF XY:

0.699

AC XY:

51435

AN XY:

73560

show subpopulations

African (AFR)

AF:

0.593

AC:

24506

AN:

41352

American (AMR)

AF:

0.777

AC:

11790

AN:

15182

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

2143

AN:

3452

East Asian (EAS)

AF:

0.763

AC:

3932

AN:

5154

South Asian (SAS)

AF:

0.738

AC:

3567

AN:

4832

European-Finnish (FIN)

AF:

0.743

AC:

7351

AN:

9898

Middle Eastern (MID)

AF:

0.616

AC:

180

AN:

292

European-Non Finnish (NFE)

AF:

0.732

AC:

49413

AN:

67466

Other (OTH)

AF:

0.681

AC:

1421

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1634

3268

4901

6535

8169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.709

Hom.:

12411

Bravo

AF:

0.693

TwinsUK

AF:

0.724

AC:

2685

ALSPAC

AF:

0.752

AC:

2897

ESP6500AA

AF:

0.627

AC:

2565

ESP6500EA

AF:

0.736

AC:

5915

ExAC

AF:

0.727

AC:

85629

Asia WGS

AF:

0.732

AC:

2456

AN:

3356

ClinVar

Significance: Benign; association

Submissions summary: Benign:2Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ADRB1-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

not provided

Benign:1

Apr 01, 2007

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

Pulmonary disease, chronic obstructive, susceptibility to

Other:1

Jul 05, 2022

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Significance:association

Review Status:no assertion criteria provided

Collection Method:research

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.66

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.34

MetaRNN

Benign

8.0e-7

MetaSVM

Benign

-0.96

PhyloP100

1.0

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

3.2

REVEL

Benign

0.070

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.055

MutPred

0.32

Gain of MoRF binding (P = 0.02)

ClinPred

0.0049

GERP RS

1.7

gMVP

0.54

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over