rs1042718

Positions:

• chr5-148827354-C-A
• chr5-148827354-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_000024.6(ADRB2):​c.523C>A​(p.Arg175=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,613,954 control chromosomes in the GnomAD database, including 32,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4561 hom., cov: 32)
  • Exomes 𝑓: 0.18 (28113 hom.)
• Consequence: ADRB2 NM_000024.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.836

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP6: Variant 5-148827354-C-A is Benign according to our data. Variant chr5-148827354-C-A is described in ClinVar as [Benign]. Clinvar id is 1264227.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.836 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADRB2	NM_000024.6	c.523C>A	p.Arg175=	synonymous_variant	1/1	ENST00000305988.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADRB2	ENST00000305988.6	c.523C>A	p.Arg175=	synonymous_variant	1/1		NM_000024.6	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34874 AN: 151988 Hom.: 4559 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.243

GnomAD3 exomes AF: 0.232 AC: 58331 AN: 251470 Hom.: 7863 AF XY: 0.228 AC XY: 30955 AN XY: 135908

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.377

Gnomad ASJ exome AF: 0.165

Gnomad EAS exome AF: 0.333

Gnomad SAS exome AF: 0.294

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.185 AC: 269780 AN: 1461848 Hom.: 28113 Cov.: 54 AF XY: 0.187 AC XY: 136087 AN XY: 727232

Gnomad4 AFR exome AF: 0.328

Gnomad4 AMR exome AF: 0.369

Gnomad4 ASJ exome AF: 0.164

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.200

GnomAD4 genome AF: 0.229 AC: 34901 AN: 152106 Hom.: 4561 Cov.: 32 AF XY: 0.229 AC XY: 17057 AN XY: 74358

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.241

Alfa AF: 0.188 Hom.: 4784

Bravo AF: 0.247

Asia WGS AF: 0.333 AC: 1158 AN: 3478

EpiCase AF: 0.182

EpiControl AF: 0.188

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	11
DANN	Benign	0.88

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: rs1042718; hg19: chr5-148206917; COSMIC: COSV60005175;