NM_000024.6:c.-47C>T

Variant names:

• chr5-148826785-C-T
• rs1042711
• NM_000024.6:c.-47C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000024.6(ADRB2):​c.-47C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,598,622 control chromosomes in the GnomAD database, including 303,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (36431 hom., cov: 34)
  • Exomes 𝑓: 0.60 (267085 hom.)
• Consequence: ADRB2 NM_000024.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.227
• Publications: 84 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 5-148826785-C-T is Benign according to our data. Variant chr5-148826785-C-T is described in ClinVar as Benign. ClinVar VariationId is 1262380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADRB2	NM_000024.6	MANE Select	c.-47C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_000015.2	X5DQM5
	ADRB2	NM_000024.6	MANE Select	c.-47C>T		5_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.-47C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000305372.4	P07550
	ADRB2	ENST00000305988.6	TSL:6 MANE Select	c.-47C>T		5_prime_UTR	Exon 1 of 1	ENSP00000305372.4	P07550
	ENSG00000303969	ENST00000798472.1		n.376+1488C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103381 AN: 152084 Hom.: 36396 Cov.: 34

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.686

GnomAD2 exomes AF: 0.684 AC: 161115 AN: 235708 AF XY: 0.678

Gnomad AFR exome AF: 0.823

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.645

Gnomad EAS exome AF: 0.907

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.599 AC: 867049 AN: 1446420 Hom.: 267085 Cov.: 43 AF XY: 0.604 AC XY: 434235 AN XY: 718964

African (AFR) AF: 0.828 AC: 27554 AN: 33262

American (AMR) AF: 0.818 AC: 36276 AN: 44370

Ashkenazi Jewish (ASJ) AF: 0.646 AC: 16762 AN: 25960

East Asian (EAS) AF: 0.901 AC: 35681 AN: 39586

South Asian (SAS) AF: 0.787 AC: 67506 AN: 85822

European-Finnish (FIN) AF: 0.589 AC: 27774 AN: 47124

Middle Eastern (MID) AF: 0.720 AC: 2977 AN: 4134

European-Non Finnish (NFE) AF: 0.556 AC: 615060 AN: 1106410

Other (OTH) AF: 0.627 AC: 37459 AN: 59752

GnomAD4 genome AF: 0.680 AC: 103477 AN: 152202 Hom.: 36431 Cov.: 34 AF XY: 0.686 AC XY: 51040 AN XY: 74410

African (AFR) AF: 0.819 AC: 34054 AN: 41562

American (AMR) AF: 0.758 AC: 11601 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2178 AN: 3472

East Asian (EAS) AF: 0.904 AC: 4665 AN: 5162

South Asian (SAS) AF: 0.794 AC: 3829 AN: 4822

European-Finnish (FIN) AF: 0.606 AC: 6424 AN: 10592

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

European-Non Finnish (NFE) AF: 0.567 AC: 38540 AN: 67972

Other (OTH) AF: 0.692 AC: 1458 AN: 2108

Alfa AF: 0.618 Hom.: 33592

Bravo AF: 0.695

Asia WGS AF: 0.842 AC: 2924 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	Beta-2-adrenoreceptor agonist, reduced response to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	15
DANN	Benign	0.94
PhyloP100		-0.23
PromoterAI		0.0028	Neutral
Mutation Taster		=192/108	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: rs1042711; hg19: chr5-148206348; COSMIC: COSV60005584;