Variant 8-37965251-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000025.3(ADRB3):c.1205+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 1,501,686 control chromosomes in the GnomAD database, including 5,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.091 ( 748 hom., cov: 33)

Exomes 𝑓: 0.084 ( 5109 hom. )

Consequence

ADRB3
NM_000025.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.323

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 8-37965251-C-A is Benign according to our data. Variant chr8-37965251-C-A is described in ClinVar as [Benign]. Clinvar id is 1230608.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRB3	NM_000025.3 linkuse as main transcript	c.1205+14G>T		intron_variant		ENST00000345060.5	NP_000016.1	P13945A8KAG8

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADRB3	ENST00000345060.5 linkuse as main transcript	c.1205+14G>T	intron_variant		1	NM_000025.3	ENSP00000343782.3	P13945
ENSG00000285880	ENST00000647937.1 linkuse as main transcript	c.689+14G>T	intron_variant				ENSP00000497740.1	A0A3B3IT50
ADRB3	ENST00000520341.2 linkuse as main transcript	n.1347G>T	non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes

AF:

0.0910

AC:

13852

AN:

152178

Hom.:

740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0808

Gnomad MID

AF:

0.0641

Gnomad NFE

AF:

0.0733

Gnomad OTH

AF:

0.0812

GnomAD3 exomes

AF:

0.0934

AC:

10921

AN:

116978

Hom.:

618

AF XY:

0.0897

AC XY:

5764

AN XY:

64266

show subpopulations

Gnomad AFR exome

AF:

0.0963

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.0310

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.123

Gnomad FIN exome

AF:

0.0770

Gnomad NFE exome

AF:

0.0663

Gnomad OTH exome

AF:

0.0836

GnomAD4 exome

AF:

0.0837

AC:

112911

AN:

1349392

Hom.:

5109

Cov.:

AF XY:

0.0840

AC XY:

55808

AN XY:

664276

show subpopulations

Gnomad4 AFR exome

AF:

0.103

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.0372

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.0819

Gnomad4 NFE exome

AF:

0.0770

Gnomad4 OTH exome

AF:

0.0862

GnomAD4 genome

AF:

0.0912

AC:

13896

AN:

152294

Hom.:

748

Cov.:

AF XY:

0.0933

AC XY:

6949

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.133

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0808

Gnomad4 NFE

AF:

0.0733

Gnomad4 OTH

AF:

0.0808

Alfa

AF:

0.0433

Hom.:

Bravo

AF:

0.0974

Asia WGS

AF:

0.143

AC:

500

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.8

DANN

Benign

0.53

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

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