Variant chr5-148827391-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000024.6(ADRB2):c.560A>G(p.Asn187Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000234 in 1,614,066 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

ADRB2
NM_000024.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.61

Variant links:

Genes affected

ADRB2 (HGNC:286): (adrenoceptor beta 2) This gene encodes beta-2-adrenergic receptor which is a member of the G protein-coupled receptor superfamily. This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(V)1.2. This receptor-channel complex also contains a G protein, an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. This receptor is also a transcription regulator of the alpha-synuclein gene, and together, both genes are believed to be associated with risk of Parkinson's Disease. This gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity, type 2 diabetes and cardiovascular disease. [provided by RefSeq, Oct 2019]

ADRB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005956948).

BP6

Variant 5-148827391-A-G is Benign according to our data. Variant chr5-148827391-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 704039.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 64 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB2	NM_000024.6 linkuse as main transcript	c.560A>G	p.Asn187Ser	missense_variant	1/1	ENST00000305988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB2	ENST00000305988.6 linkuse as main transcript	c.560A>G	p.Asn187Ser	missense_variant	1/1		NM_000024.6	P1

Frequencies

GnomAD3 genomes

AF:

0.000421

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00462

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000513

AC:

129

AN:

251486

Hom.:

AF XY:

0.000419

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00130

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00411

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000215

AC:

314

AN:

1461814

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

156

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000554

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00459

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000420

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000524

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00462

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000663

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.20

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.44

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Benign

0.0075

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.9

REVEL

Benign

0.13

Sift

Uncertain

0.0060

Sift4G

Benign

0.21

Polyphen

0.013

Vest4

0.076

MVP

0.54

MPC

0.41

ClinPred

0.056

GERP RS

3.3

Varity_R

0.12

gMVP

0.27

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