Genetic Variant ADRB3:c.1206-96A>G (chr8-37964335-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000025.3(ADRB3):c.1206-96A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 1,143,280 control chromosomes in the GnomAD database, including 5,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 747 hom., cov: 32)

Exomes 𝑓: 0.084 ( 4269 hom. )

Consequence

ADRB3
NM_000025.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.198

Publications

2 publications found

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:

ENSG00000285880 (HGNC:):

ENSG00000285880 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 8-37964335-T-C is Benign according to our data. Variant chr8-37964335-T-C is described in ClinVar as [Benign]. Clinvar id is 1244998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB3	NM_000025.3 link	c.1206-96A>G		intron_variant	Intron 1 of 1	ENST00000345060.5	NP_000016.1	P13945A8KAG8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB3	ENST00000345060.5 link	c.1206-96A>G		intron_variant	Intron 1 of 1	1	NM_000025.3	ENSP00000343782.3		P13945
ENSG00000285880	ENST00000647937.1 link	c.689+930A>G		intron_variant	Intron 1 of 1			ENSP00000497740.1		A0A3B3IT50

Frequencies

GnomAD3 genomes

AF:

0.0911

AC:

13835

AN:

151866

Hom.:

738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0361

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0807

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0732

Gnomad OTH

AF:

0.0815

GnomAD4 exome

AF:

0.0844

AC:

83709

AN:

991294

Hom.:

4269

AF XY:

0.0847

AC XY:

43019

AN XY:

507970

show subpopulations

African (AFR)

AF:

0.104

AC:

2424

AN:

23396

American (AMR)

AF:

0.191

AC:

6734

AN:

35294

Ashkenazi Jewish (ASJ)

AF:

0.0367

AC:

808

AN:

22016

East Asian (EAS)

AF:

0.166

AC:

5941

AN:

35746

South Asian (SAS)

AF:

0.120

AC:

8549

AN:

71378

European-Finnish (FIN)

AF:

0.0816

AC:

4059

AN:

49722

Middle Eastern (MID)

AF:

0.0651

AC:

301

AN:

4622

European-Non Finnish (NFE)

AF:

0.0727

AC:

51192

AN:

704598

Other (OTH)

AF:

0.0831

AC:

3701

AN:

44522

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3653

7307

10960

14614

18267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0913

AC:

13880

AN:

151986

Hom.:

747

Cov.:

AF XY:

0.0934

AC XY:

6940

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.104

AC:

4327

AN:

41452

American (AMR)

AF:

0.134

AC:

2040

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0361

AC:

125

AN:

3464

East Asian (EAS)

AF:

0.144

AC:

740

AN:

5142

South Asian (SAS)

AF:

0.127

AC:

612

AN:

4812

European-Finnish (FIN)

AF:

0.0807

AC:

853

AN:

10574

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0732

AC:

4976

AN:

67952

Other (OTH)

AF:

0.0811

AC:

171

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

641

1283

1924

2566

3207

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0354

Hom.:

Bravo

AF:

0.0975

Asia WGS

AF:

0.142

AC:

497

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 18, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.2

(source)

DANN

Benign

0.62

PhyloP100

-0.20

Mutation Taster

=100/0

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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chr8-37964335-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over