Variant 8-37965685-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000345060.5(ADRB3):c.785C>A(p.Pro262Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,386,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P262R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADRB3
ENST00000345060.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0330

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06392786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRB3	NM_000025.3 linkuse as main transcript	c.785C>A	p.Pro262Gln	missense_variant	1/2	ENST00000345060.5	NP_000016.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRB3	ENST00000345060.5 linkuse as main transcript	c.785C>A	p.Pro262Gln	missense_variant	1/2	1	NM_000025.3	ENSP00000343782	P1
ADRB3	ENST00000520341.2 linkuse as main transcript	n.913C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000150

AC:

AN:

133564

Hom.:

AF XY:

0.0000278

AC XY:

AN XY:

71990

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000860

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000144

AC:

AN:

1386836

Hom.:

Cov.:

AF XY:

0.00000293

AC XY:

AN XY:

683216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000579

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 04, 2024

The c.785C>A (p.P262Q) alteration is located in exon 1 (coding exon 1) of the ADRB3 gene. This alteration results from a C to A substitution at nucleotide position 785, causing the proline (P) at amino acid position 262 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.54

CADD

Benign

1.8

DANN

Benign

0.63

DEOGEN2

Benign

0.073

.;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.70

.;N

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.27

.;N

REVEL

Benign

0.15

Sift

Benign

0.23

.;T

Sift4G

Benign

0.69

.;T

Polyphen

0.0020

.;B

Vest4

0.097

MutPred

0.30

.;Loss of loop (P = 0.0804);

MVP

0.44

MPC

0.79

ClinPred

0.088

GERP RS

-5.2

Varity_R

0.031

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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