rs1042720

Variant names:

• chr5-148828070-G-A
• rs1042720
• NM_000024.6:c.1239G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-148828070-G-A
• chr5-148828070-G-C
• chr5-148828070-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000024.6(ADRB2):​c.1239G>A​(p.Leu413Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,558,986 control chromosomes in the GnomAD database, including 98,929 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L413L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.41 (13365 hom., cov: 28)
  • Exomes 𝑓: 0.34 (85564 hom.)
• Consequence: ADRB2 NM_000024.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.149
• Publications: 28 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 5-148828070-G-A is Benign according to our data. Variant chr5-148828070-G-A is described in ClinVar as Benign. ClinVar VariationId is 1256688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.149 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.605 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.1239G>A	p.Leu413Leu	synonymous	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.1239G>A	p.Leu413Leu	synonymous	Exon 1 of 1	ENSP00000305372.4
	ENSG00000303969	ENST00000798472.1		n.376+2773G>A		intron	N/A
	ENSG00000303969	ENST00000798473.1		n.349+2773G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.408 AC: 60633 AN: 148694 Hom.: 13341 Cov.: 28

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.474

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.379 AC: 82262 AN: 216920 AF XY: 0.375

Gnomad AFR exome AF: 0.539

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.290

Gnomad EAS exome AF: 0.613

Gnomad FIN exome AF: 0.262

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.340 AC: 479101 AN: 1410178 Hom.: 85564 Cov.: 36 AF XY: 0.342 AC XY: 238940 AN XY: 698318

African (AFR) AF: 0.541 AC: 17124 AN: 31630

American (AMR) AF: 0.465 AC: 17135 AN: 36848

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 7787 AN: 23086

East Asian (EAS) AF: 0.611 AC: 23792 AN: 38936

South Asian (SAS) AF: 0.476 AC: 36995 AN: 77678

European-Finnish (FIN) AF: 0.280 AC: 14259 AN: 51012

Middle Eastern (MID) AF: 0.441 AC: 2396 AN: 5430

European-Non Finnish (NFE) AF: 0.311 AC: 338443 AN: 1087504

Other (OTH) AF: 0.365 AC: 21170 AN: 58054

GnomAD4 genome AF: 0.408 AC: 60690 AN: 148808 Hom.: 13365 Cov.: 28 AF XY: 0.409 AC XY: 29544 AN XY: 72288

African (AFR) AF: 0.542 AC: 21930 AN: 40452

American (AMR) AF: 0.453 AC: 6758 AN: 14906

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1159 AN: 3466

East Asian (EAS) AF: 0.624 AC: 3033 AN: 4864

South Asian (SAS) AF: 0.507 AC: 2370 AN: 4674

European-Finnish (FIN) AF: 0.278 AC: 2688 AN: 9668

Middle Eastern (MID) AF: 0.476 AC: 139 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21490 AN: 67498

Other (OTH) AF: 0.423 AC: 878 AN: 2076

Alfa AF: 0.362 Hom.: 6135

Bravo AF: 0.424

Asia WGS AF: 0.534 AC: 1856 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.9
DANN	Benign	0.72
PhyloP100		0.15
Mutation Taster		=100/0	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: rs1042720; hg19: chr5-148207633; COSMIC: COSV60005554;