dbSNP rs1042720: ADRB2:p.Leu413Leu (chr5-148828070-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_000024.6(ADRB2):c.1239G>A(p.Leu413Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,558,986 control chromosomes in the GnomAD database, including 98,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 13365 hom., cov: 28)

Exomes 𝑓: 0.34 ( 85564 hom. )

Consequence

ADRB2
NM_000024.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.149

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 5-148828070-G-A is Benign according to our data. Variant chr5-148828070-G-A is described in ClinVar as [Benign]. Clinvar id is 1256688.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.149 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6 link	c.1239G>A	p.Leu413Leu	synonymous_variant	Exon 1 of 1	ENST00000305988.6	NP_000015.2	P07550X5DQM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB2	ENST00000305988.6 link	c.1239G>A	p.Leu413Leu	synonymous_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4		P07550

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

60633

AN:

148694

Hom.:

13341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.542

Gnomad AMI

AF:

0.269

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.624

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.278

Gnomad MID

AF:

0.474

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.425

GnomAD3 exomes

AF:

0.379

AC:

82262

AN:

216920

Hom.:

17075

AF XY:

0.375

AC XY:

43689

AN XY:

116546

show subpopulations

Gnomad AFR exome

AF:

0.539

Gnomad AMR exome

AF:

0.464

Gnomad ASJ exome

AF:

0.290

Gnomad EAS exome

AF:

0.613

Gnomad SAS exome

AF:

0.447

Gnomad FIN exome

AF:

0.262

Gnomad NFE exome

AF:

0.311

Gnomad OTH exome

AF:

0.359

GnomAD4 exome

AF:

0.340

AC:

479101

AN:

1410178

Hom.:

85564

Cov.:

AF XY:

0.342

AC XY:

238940

AN XY:

698318

show subpopulations

Gnomad4 AFR exome

AF:

0.541

Gnomad4 AMR exome

AF:

0.465

Gnomad4 ASJ exome

AF:

0.337

Gnomad4 EAS exome

AF:

0.611

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.280

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.365

GnomAD4 genome

AF:

0.408

AC:

60690

AN:

148808

Hom.:

13365

Cov.:

AF XY:

0.409

AC XY:

29544

AN XY:

72288

show subpopulations

Gnomad4 AFR

AF:

0.542

Gnomad4 AMR

AF:

0.453

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.624

Gnomad4 SAS

AF:

0.507

Gnomad4 FIN

AF:

0.278

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.349

Hom.:

4130

Bravo

AF:

0.424

Asia WGS

AF:

0.534

AC:

1856

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

-0.63

CADD

Benign

3.9

DANN

Benign

0.72

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