NM_000024.6:c.13G>C

Variant names:

• chr5-148826844-G-C
• rs748833484
• NM_000024.6:c.13G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000024.6(ADRB2):​c.13G>C​(p.Gly5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: ADRB2 NM_000024.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16475552).

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.13G>C	p.Gly5Arg	missense	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.13G>C	p.Gly5Arg	missense	Exon 1 of 1	ENSP00000305372.4	P07550
	ENSG00000303969	ENST00000798472.1		n.376+1547G>C		intron	N/A
	ENSG00000303969	ENST00000798473.1		n.349+1547G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 70

GnomAD4 genome Cov.: 35

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	ADRB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.97	L
PhyloP100		2.7
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.058
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.094	T
Polyphen		0.0080	B
Vest4		0.13
MutPred		0.30		Gain of solvent accessibility (P = 0.0097)
MVP		0.64
MPC		1.0
ClinPred		0.45	T
GERP RS		2.9
PromoterAI		0.070	Neutral
Varity_R		0.12
gMVP		0.72
Mutation Taster		=84/16	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: rs748833484; hg19: chr5-148206407;