Variant 10-114045297-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,association (no stars).

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRB1	NM_000684.3 linkuse as main transcript	c.1165G>C	p.Gly389Arg	missense_variant	1/1	ENST00000369295.4	NP_000675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRB1	ENST00000369295.4 linkuse as main transcript	c.1165G>C	p.Gly389Arg	missense_variant	1/1		NM_000684.3	ENSP00000358301	P1

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

GnomAD3 exomes

AF:

0.737

AC:

162149

AN:

219864

Hom.:

60356

AF XY:

0.735

AC XY:

89178

AN XY:

121330

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 SAS exome

AF:

0.754

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

Gnomad4 AFR exome

AF:

0.579

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.620

Gnomad4 EAS exome

AF:

0.781

Gnomad4 SAS exome

AF:

0.755

Gnomad4 FIN exome

AF:

0.746

Gnomad4 NFE exome

AF:

0.735

Gnomad4 OTH exome

AF:

0.720

GnomAD4 genome

AF:

0.696

AC:

104861

AN:

150622

Hom.:

36948

Cov.:

AF XY:

0.699

AC XY:

51435

AN XY:

73560

show subpopulations

Gnomad4 AFR

AF:

0.593

Gnomad4 AMR

AF:

0.777

Gnomad4 ASJ

AF:

0.621

Gnomad4 EAS

AF:

0.763

Gnomad4 SAS

AF:

0.738

Gnomad4 FIN

AF:

0.743

Gnomad4 NFE

AF:

0.732

Gnomad4 OTH

AF:

0.681

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

Benign, no assertion criteria provided

literature only

OMIM

Apr 01, 2007

- -

Pulmonary disease, chronic obstructive, susceptibility to

Other:1

association, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Jul 05, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

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

MutationTaster

Benign

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over