5-148826785-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000024.6(ADRB2):c.-47C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,598,622 control chromosomes in the GnomAD database, including 303,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (36431 hom., cov: 34)
  • Exomes 𝑓: 0.60 (267085 hom.)
• Consequence: ADRB2 NM_000024.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.227

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-148826785-C-T is Benign according to our data. Variant chr5-148826785-C-T is described in ClinVar as [Benign]. Clinvar id is 1262380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB2	NM_000024.6	c.-47C>T		5_prime_UTR_variant	1/1	ENST00000305988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB2	ENST00000305988.6	c.-47C>T		5_prime_UTR_variant	1/1		NM_000024.6	P1

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103381 AN: 152084 Hom.: 36396 Cov.: 34

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.686

GnomAD3 exomes AF: 0.684 AC: 161115 AN: 235708 Hom.: 57130 AF XY: 0.678 AC XY: 87468 AN XY: 128916

Gnomad AFR exome AF: 0.823

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.645

Gnomad EAS exome AF: 0.907

Gnomad SAS exome AF: 0.790

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.599 AC: 867049 AN: 1446420 Hom.: 267085 Cov.: 43 AF XY: 0.604 AC XY: 434235 AN XY: 718964

Gnomad4 AFR exome AF: 0.828

Gnomad4 AMR exome AF: 0.818

Gnomad4 ASJ exome AF: 0.646

Gnomad4 EAS exome AF: 0.901

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.589

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.627

GnomAD4 genome AF: 0.680 AC: 103477 AN: 152202 Hom.: 36431 Cov.: 34 AF XY: 0.686 AC XY: 51040 AN XY: 74410

Gnomad4 AFR AF: 0.819

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.904

Gnomad4 SAS AF: 0.794

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.567

Gnomad4 OTH AF: 0.692

Alfa AF: 0.609 Hom.: 23312

Bravo AF: 0.695

Asia WGS AF: 0.842 AC: 2924 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

This variant is associated with the following publications: (PMID: 10323412, 21801278) -

Beta-2-adrenoreceptor agonist, reduced response to Other:1

drug response, no assertion criteria provided

literature only

OMIM

Jun 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	15
Dann	Benign	0.94

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

Other links and lift over

dbSNP: rs1042711; hg19: chr5-148206348; COSMIC: COSV60005584;