rs45580732

Variant names:

• chr5-148828099-C-CA
• rs45580732
• NM_000024.6:c.*26_*27insA

Your query was ambiguous. Multiple possible variants found:

• chr5-148828099-C-CA
• chr5-148828099-C-CG
• chr5-148828099-C-CT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000024.6(ADRB2):​c.*26_*27insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 1,280,390 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000010 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ADRB2 NM_000024.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.185
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6	c.*26_*27insA		3_prime_UTR_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.*26_*27insA		3_prime_UTR_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4
ENSG00000303969	ENST00000798472.1	n.376+2802_376+2803insA		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1	n.349+2802_349+2803insA		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.0000101 AC: 1 AN: 98850 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000131

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000148 AC: 2 AN: 135490 AF XY: 0.0000273

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000137

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000339 AC: 4 AN: 1181540 Hom.: 0 Cov.: 26 AF XY: 0.00000338 AC XY: 2 AN XY: 592430

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28442

American (AMR) AF: 0.0000307 AC: 1 AN: 32608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20358

East Asian (EAS) AF: 0.00 AC: 0 AN: 37870

South Asian (SAS) AF: 0.00 AC: 0 AN: 70868

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.00000339 AC: 3 AN: 885698

Other (OTH) AF: 0.00 AC: 0 AN: 50632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0129288), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000101 AC: 1 AN: 98850 Hom.: 0 Cov.: 28 AF XY: 0.0000211 AC XY: 1 AN XY: 47312

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15900

American (AMR) AF: 0.00 AC: 0 AN: 9952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2780

East Asian (EAS) AF: 0.00 AC: 0 AN: 2336

South Asian (SAS) AF: 0.00 AC: 0 AN: 2276

European-Finnish (FIN) AF: 0.000131 AC: 1 AN: 7654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55634

Other (OTH) AF: 0.00 AC: 0 AN: 1416

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

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: rs45580732; hg19: chr5-148207662;