NM_000024.6:c.*26C>A

Variant names:

• chr5-148828099-C-A
• rs28763957
• NM_000024.6:c.*26C>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_000024.6(ADRB2):​c.*26C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000405 in 1,280,378 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: ADRB2 NM_000024.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 2 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAd4 at 28 AD gene.

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.*26C>A		3_prime_UTR	Exon 1 of 1	NP_000015.2

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 28 AN: 98850 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000360

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000431

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000406 AC: 55 AN: 135490 AF XY: 0.000354

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000239

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000128

Gnomad NFE exome AF: 0.000671

Gnomad OTH exome AF: 0.000862

GnomAD4 exome AF: 0.000415 AC: 490 AN: 1181528 Hom.: 6 Cov.: 25 AF XY: 0.000387 AC XY: 229 AN XY: 592428

African (AFR) AF: 0.000105 AC: 3 AN: 28442

American (AMR) AF: 0.00 AC: 0 AN: 32608

Ashkenazi Jewish (ASJ) AF: 0.000246 AC: 5 AN: 20358

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 70870

European-Finnish (FIN) AF: 0.0000998 AC: 5 AN: 50116

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

European-Non Finnish (NFE) AF: 0.000493 AC: 437 AN: 885684

Other (OTH) AF: 0.000790 AC: 40 AN: 50632

GnomAD4 genome AF: 0.000283 AC: 28 AN: 98850 Hom.: 0 Cov.: 27 AF XY: 0.000380 AC XY: 18 AN XY: 47312

African (AFR) AF: 0.000189 AC: 3 AN: 15900

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

Ashkenazi Jewish (ASJ) AF: 0.000360 AC: 1 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: 0.00 AC: 0 AN: 7654

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

European-Non Finnish (NFE) AF: 0.000431 AC: 24 AN: 55634

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.58
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism

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: rs28763957; hg19: chr5-148207662;