rs1042718

Variant names:

• chr5-148827354-C-A
• rs1042718
• NM_000024.6:c.523C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_000024.6(ADRB2):​c.523C>A​(p.Arg175Arg) 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
• Publications: 86 publications found

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]

ENSG00000303969 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ADRB2	NM_000024.6	c.523C>A	p.Arg175Arg	synonymous_variant	Exon 1 of 1	ENST00000305988.6	NP_000015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB2	ENST00000305988.6	c.523C>A	p.Arg175Arg	synonymous_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4
ENSG00000303969	ENST00000798472.1	n.376+2057C>A		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1	n.349+2057C>A		intron_variant	Intron 3 of 4

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

GnomAD2 exomes AF: 0.232 AC: 58331 AN: 251470 AF XY: 0.228

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 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

African (AFR) AF: 0.328 AC: 10988 AN: 33480

American (AMR) AF: 0.369 AC: 16497 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 4291 AN: 26134

East Asian (EAS) AF: 0.368 AC: 14596 AN: 39698

South Asian (SAS) AF: 0.294 AC: 25317 AN: 86254

European-Finnish (FIN) AF: 0.131 AC: 7012 AN: 53414

Middle Eastern (MID) AF: 0.266 AC: 1535 AN: 5768

European-Non Finnish (NFE) AF: 0.160 AC: 177441 AN: 1111980

Other (OTH) AF: 0.200 AC: 12103 AN: 60396

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

African (AFR) AF: 0.318 AC: 13204 AN: 41476

American (AMR) AF: 0.299 AC: 4577 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1790 AN: 5160

South Asian (SAS) AF: 0.308 AC: 1484 AN: 4818

European-Finnish (FIN) AF: 0.121 AC: 1287 AN: 10598

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11139 AN: 67982

Other (OTH) AF: 0.241 AC: 510 AN: 2112

Alfa AF: 0.193 Hom.: 6320

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

Jun 09, 2021

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	-0.33
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.84
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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