chr5-148826910-G-C

Variant names:

• chr5-148826910-G-C
• rs1042714
• NM_000024.6:c.79G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000024.6(ADRB2):​c.79G>C​(p.Glu27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 1,613,984 control chromosomes in the GnomAD database, including 308,381 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.68 (36699 hom., cov: 34)
  • Exomes 𝑓: 0.60 (271682 hom.)
• Consequence: ADRB2 NM_000024.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 857 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.058008E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB2	NM_000024.6	MANE Select	c.79G>C	p.Glu27Gln	missense	Exon 1 of 1	NP_000015.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB2	ENST00000305988.6	TSL:6 MANE Select	c.79G>C	p.Glu27Gln	missense	Exon 1 of 1	ENSP00000305372.4
	ENSG00000303969	ENST00000798472.1		n.376+1613G>C		intron	N/A
	ENSG00000303969	ENST00000798473.1		n.349+1613G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103807 AN: 152130 Hom.: 36668 Cov.: 34

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.683 AC: 171840 AN: 251422 AF XY: 0.679

Gnomad AFR exome AF: 0.822

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.646

Gnomad EAS exome AF: 0.909

Gnomad FIN exome AF: 0.615

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.657

GnomAD4 exome AF: 0.601 AC: 879112 AN: 1461736 Hom.: 271682 Cov.: 67 AF XY: 0.606 AC XY: 440572 AN XY: 727160

African (AFR) AF: 0.829 AC: 27748 AN: 33480

American (AMR) AF: 0.818 AC: 36563 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 16909 AN: 26136

East Asian (EAS) AF: 0.921 AC: 36568 AN: 39700

South Asian (SAS) AF: 0.787 AC: 67833 AN: 86246

European-Finnish (FIN) AF: 0.613 AC: 32760 AN: 53418

Middle Eastern (MID) AF: 0.723 AC: 4130 AN: 5716

European-Non Finnish (NFE) AF: 0.556 AC: 618618 AN: 1111936

Other (OTH) AF: 0.629 AC: 37983 AN: 60380

GnomAD4 genome AF: 0.682 AC: 103899 AN: 152248 Hom.: 36699 Cov.: 34 AF XY: 0.689 AC XY: 51309 AN XY: 74450

African (AFR) AF: 0.820 AC: 34079 AN: 41562

American (AMR) AF: 0.758 AC: 11597 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2182 AN: 3472

East Asian (EAS) AF: 0.909 AC: 4693 AN: 5162

South Asian (SAS) AF: 0.794 AC: 3839 AN: 4832

European-Finnish (FIN) AF: 0.632 AC: 6697 AN: 10602

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38617 AN: 67996

Other (OTH) AF: 0.694 AC: 1468 AN: 2116

Alfa AF: 0.603 Hom.: 9136

Bravo AF: 0.695

TwinsUK AF: 0.556 AC: 2061

ALSPAC AF: 0.565 AC: 2178

ESP6500AA AF: 0.816 AC: 3597

ESP6500EA AF: 0.580 AC: 4987

ExAC AF: 0.683 AC: 82958

Asia WGS AF: 0.843 AC: 2927 AN: 3478

EpiCase AF: 0.584

EpiControl AF: 0.589

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	16
DANN	Benign	0.77
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.79	T
MetaRNN	Benign	7.1e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.023
Sift	Benign	0.41	T
Sift4G	Benign	0.57	T
Polyphen		0.0090	B
Vest4		0.033
MPC		0.52
ClinPred		0.0077	T
GERP RS		4.0
PromoterAI		-0.10	Neutral
Varity_R		0.063
gMVP		0.35
Mutation Taster		=95/5	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: rs1042714; hg19: chr5-148206473; COSMIC: COSV60005978;