Genetic Variant ADRB3:c.1205+320dupT (chr8-37964944-T-TA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_000025.3(ADRB3):c.1205+320dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 243,232 control chromosomes in the GnomAD database, including 633 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.090 ( 630 hom., cov: 31)

Exomes 𝑓: 0.084 ( 3 hom. )

Consequence

ADRB3
NM_000025.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.114

Publications

0 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 -10 ACMG points.

BP6

Variant 8-37964944-T-TA is Benign according to our data. Variant chr8-37964944-T-TA is described in ClinVar as [Benign]. Clinvar id is 1288105.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB3	NM_000025.3 link	c.1205+320dupT		intron_variant	Intron 1 of 1	ENST00000345060.5	NP_000016.1	P13945A8KAG8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADRB3	ENST00000345060.5 link	c.1205+320dupT	intron_variant	Intron 1 of 1	1	NM_000025.3	ENSP00000343782.3	P13945
ENSG00000285880	ENST00000647937.1 link	c.689+320dupT	intron_variant	Intron 1 of 1			ENSP00000497740.1	A0A3B3IT50
ADRB3	ENST00000520341.2 link	n.*29dupT	downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0896

AC:

12931

AN:

144390

Hom.:

630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0977

Gnomad AMI

AF:

0.0293

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.131

Gnomad FIN

AF:

0.0602

Gnomad MID

AF:

0.0888

Gnomad NFE

AF:

0.0750

Gnomad OTH

AF:

0.0822

GnomAD4 exome

AF:

0.0836

AC:

8259

AN:

98780

Hom.:

Cov.:

AF XY:

0.0829

AC XY:

4091

AN XY:

49336

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0958

AC:

293

AN:

3060

American (AMR)

AF:

0.134

AC:

347

AN:

2580

Ashkenazi Jewish (ASJ)

AF:

0.0538

AC:

201

AN:

3734

East Asian (EAS)

AF:

0.152

AC:

1124

AN:

7406

South Asian (SAS)

AF:

0.0939

AC:

226

AN:

2408

European-Finnish (FIN)

AF:

0.0710

AC:

401

AN:

5650

Middle Eastern (MID)

AF:

0.0813

AC:

AN:

566

European-Non Finnish (NFE)

AF:

0.0761

AC:

5060

AN:

66458

Other (OTH)

AF:

0.0811

AC:

561

AN:

6918

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.385

Heterozygous variant carriers

409

818

1227

1636

2045

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0897

AC:

12953

AN:

144452

Hom.:

630

Cov.:

AF XY:

0.0906

AC XY:

6356

AN XY:

70158

show subpopulations

African (AFR)

AF:

0.0980

AC:

3858

AN:

39372

American (AMR)

AF:

0.136

AC:

1983

AN:

14608

Ashkenazi Jewish (ASJ)

AF:

0.0378

AC:

127

AN:

3360

East Asian (EAS)

AF:

0.147

AC:

722

AN:

4920

South Asian (SAS)

AF:

0.131

AC:

592

AN:

4530

European-Finnish (FIN)

AF:

0.0602

AC:

534

AN:

8868

Middle Eastern (MID)

AF:

0.0929

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.0750

AC:

4920

AN:

65616

Other (OTH)

AF:

0.0821

AC:

165

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

559

1118

1678

2237

2796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0161

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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chr8-37964944-T-TA

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