5-148828099-C-CT

Variant names:

• chr5-148828099-C-CT
• rs45580732
• NM_000024.6:c.*26_*27insT

Variant summary

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

The NM_000024.6(ADRB2):​c.*26_*27insT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000169 in 1,181,542 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: not found (cov: 28)
  • Exomes 𝑓: 0.0000017 (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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000024.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB2	NM_000024.6	MANE Select	c.*26_*27insT		3_prime_UTR	Exon 1 of 1	NP_000015.2	X5DQM5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB2	ENST00000305988.6	TSL:6 MANE Select	c.*26_*27insT		3_prime_UTR	Exon 1 of 1	ENSP00000305372.4	P07550
	ENSG00000303969	ENST00000798472.1		n.376+2802_376+2803insT		intron	N/A
	ENSG00000303969	ENST00000798473.1		n.349+2802_349+2803insT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00000738 AC: 1 AN: 135490 AF XY: 0.0000136

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000169 AC: 2 AN: 1181542 Hom.: 0 Cov.: 26 AF XY: 0.00000169 AC XY: 1 AN XY: 592432

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

American (AMR) AF: 0.00 AC: 0 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: 0.0000282 AC: 2 AN: 70870

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: 0.00 AC: 0 AN: 885698

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

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;