Genetic Variant ADRB2:c.-367C>T (chr5-148826465-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000024.6(ADRB2):c.-367C>T variant causes a upstream gene change. The variant allele was found at a frequency of 0.651 in 338,212 control chromosomes in the GnomAD database, including 74,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.68 ( 36691 hom., cov: 33)

Exomes 𝑓: 0.63 ( 38161 hom. )

Consequence

ADRB2
NM_000024.6 upstream_gene

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.64

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 5-148826465-C-T is Benign according to our data. Variant chr5-148826465-C-T is described in ClinVar as [Benign]. Clinvar id is 1259578.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6 link	c.-367C>T		upstream_gene_variant		ENST00000305988.6	NP_000015.2	P07550X5DQM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB2	ENST00000305988.6 link	c.-367C>T		upstream_gene_variant		6	NM_000024.6	ENSP00000305372.4		P07550

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103748

AN:

151994

Hom.:

36660

Cov.:

show subpopulations

Gnomad AFR

AF:

0.821

Gnomad AMI

AF:

0.555

Gnomad AMR

AF:

0.758

Gnomad ASJ

AF:

0.629

Gnomad EAS

AF:

0.909

Gnomad SAS

AF:

0.793

Gnomad FIN

AF:

0.632

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.568

Gnomad OTH

AF:

0.688

GnomAD4 exome

AF:

0.625

AC:

116365

AN:

186100

Hom.:

38161

Cov.:

AF XY:

0.635

AC XY:

62263

AN XY:

98036

show subpopulations

Gnomad4 AFR exome

AF:

0.829

Gnomad4 AMR exome

AF:

0.790

Gnomad4 ASJ exome

AF:

0.632

Gnomad4 EAS exome

AF:

0.915

Gnomad4 SAS exome

AF:

0.783

Gnomad4 FIN exome

AF:

0.600

Gnomad4 NFE exome

AF:

0.552

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.683

AC:

103840

AN:

152112

Hom.:

36691

Cov.:

AF XY:

0.689

AC XY:

51260

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.820

Gnomad4 AMR

AF:

0.759

Gnomad4 ASJ

AF:

0.629

Gnomad4 EAS

AF:

0.909

Gnomad4 SAS

AF:

0.794

Gnomad4 FIN

AF:

0.632

Gnomad4 NFE

AF:

0.568

Gnomad4 OTH

AF:

0.694

Alfa

AF:

0.623

Hom.:

3799

Bravo

AF:

0.696

Asia WGS

AF:

0.845

AC:

2934

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 10, 2018

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

-0.69

CADD

Benign

DANN

Benign

0.93

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