rs4994

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000025.3(ADRB3):c.190T>C(p.Trp64Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 1,613,570 control chromosomes in the GnomAD database, including 7,132 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.093 ( 769 hom., cov: 33)

Exomes 𝑓: 0.088 ( 6363 hom. )

Consequence

ADRB3
NM_000025.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 1.05

Variant links:

Genes affected

ADRB3 (HGNC:288): (adrenoceptor beta 3) The protein encoded by this gene belongs to the family of beta adrenergic receptors, which mediate catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor is located mainly in the adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Obesity and bodyweight-related disorders are correlated with certain polymorphisms in three subtypes of beta-adrenoceptor, among them, the ADRB3 gene.[provided by RefSeq, Oct 2019]

ADRB3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.1804395E-4).

BP6

Variant 8-37966280-A-G is Benign according to our data. Variant chr8-37966280-A-G is described in ClinVar as [Benign]. Clinvar id is 17741.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB3	NM_000025.3 linkuse as main transcript	c.190T>C	p.Trp64Arg	missense_variant	1/2	ENST00000345060.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB3	ENST00000345060.5 linkuse as main transcript	c.190T>C	p.Trp64Arg	missense_variant	1/2	1	NM_000025.3	P1
ADRB3	ENST00000520341.2 linkuse as main transcript	n.318T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0927

AC:

14099

AN:

152152

Hom.:

761

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0487

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0806

Gnomad MID

AF:

0.0796

Gnomad NFE

AF:

0.0745

Gnomad OTH

AF:

0.0847

GnomAD3 exomes

AF:

0.106

AC:

26242

AN:

247172

Hom.:

1769

AF XY:

0.103

AC XY:

13824

AN XY:

134230

show subpopulations

Gnomad AFR exome

AF:

0.107

Gnomad AMR exome

AF:

0.205

Gnomad ASJ exome

AF:

0.0482

Gnomad EAS exome

AF:

0.142

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0791

Gnomad NFE exome

AF:

0.0742

Gnomad OTH exome

AF:

0.0967

GnomAD4 exome

AF:

0.0880

AC:

128533

AN:

1461300

Hom.:

6363

Cov.:

AF XY:

0.0882

AC XY:

64153

AN XY:

726968

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.197

Gnomad4 ASJ exome

AF:

0.0499

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.0826

Gnomad4 NFE exome

AF:

0.0783

Gnomad4 OTH exome

AF:

0.0895

GnomAD4 genome

AF:

0.0929

AC:

14139

AN:

152270

Hom.:

769

Cov.:

AF XY:

0.0952

AC XY:

7087

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.138

Gnomad4 ASJ

AF:

0.0487

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0806

Gnomad4 NFE

AF:

0.0745

Gnomad4 OTH

AF:

0.0843

Alfa

AF:

0.0759

Hom.:

930

Bravo

AF:

0.0992

TwinsUK

AF:

0.0720

AC:

267

ALSPAC

AF:

0.0758

AC:

292

ESP6500AA

AF:

0.106

AC:

468

ESP6500EA

AF:

0.0756

AC:

649

ExAC

AF:

0.102

AC:

12436

Asia WGS

AF:

0.144

AC:

506

AN:

3478

EpiCase

AF:

0.0700

EpiControl

AF:

0.0707

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

This variant is associated with the following publications: (PMID: 9080262, 29670643, 22774474, 11380082, 21529759, 23729572, 21289629, 21358132, 20008926, 20069060, 11564599, 17225053, 19553224, 22550477, 19133996, 21285172, 21034552, 19080138, 7487991, 28456594, 23968135, 20078877, 23032405) -

Obesity

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Oct 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.44

DEOGEN2

Benign

0.044

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.39

MetaRNN

Benign

0.00082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.58

PROVEAN

Benign

6.1

REVEL

Benign

0.12

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.019

MutPred

0.23

Gain of methylation at W64 (P = 0.0847);

MPC

1.4

ClinPred

0.0028

GERP RS

2.4

Varity_R

0.11

gMVP

0.40

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