Genetic Variant ADRB2:c.*26C>G (chr5-148828099-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000024.6(ADRB2):c.*26C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000203 in 1,280,388 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000061 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ADRB2
NM_000024.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6 link	c.*26C>G		3_prime_UTR_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.*26C>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4		P07550

Frequencies

GnomAD3 genomes

AF:

0.0000607

AC:

AN:

98850

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000100

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000180

Gnomad OTH

AF:

0.00141

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

135490

Hom.:

AF XY:

0.0000273

AC XY:

AN XY:

73356

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000648

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:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000169

AC:

AN:

1181538

Hom.:

Cov.:

AF XY:

0.0000203

AC XY:

AN XY:

592428

show subpopulations

Gnomad4 AFR exome

AF:

0.0000703

Gnomad4 AMR exome

AF:

0.0000613

Gnomad4 ASJ exome

AF:

0.0000491

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000282

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000102

Gnomad4 OTH exome

AF:

0.0000790

GnomAD4 genome

AF:

0.0000607

AC:

AN:

98850

Hom.:

Cov.:

AF XY:

0.0000423

AC XY:

AN XY:

47312

show subpopulations

Gnomad4 AFR

AF:

0.000126

Gnomad4 AMR

AF:

0.000100

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000180

Gnomad4 OTH

AF:

0.00141

Alfa

AF:

0.0000642

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.4

DANN

Benign

0.62

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over