5-148826812-C-T

Variant names:

• chr5-148826812-C-T
• rs1801704
• NM_000024.6:c.-20C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000024.6(ADRB2):​c.-20C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 1,609,660 control chromosomes in the GnomAD database, including 305,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (36434 hom., cov: 35)
  • Exomes 𝑓: 0.60 (268942 hom.)
• Consequence: ADRB2 NM_000024.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.29
• Publications: 49 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 (BayesDel_noAF=-0.38).
• BP6: Variant 5-148826812-C-T is Benign according to our data. Variant chr5-148826812-C-T is described in ClinVar as Benign. ClinVar VariationId is 1297319.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6	c.-20C>T		5_prime_UTR_variant	Exon 1 of 1	ENST00000305988.6	NP_000015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB2	ENST00000305988.6	c.-20C>T		5_prime_UTR_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4
ENSG00000303969	ENST00000798472.1	n.376+1515C>T		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1	n.349+1515C>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103410 AN: 152130 Hom.: 36403 Cov.: 35

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.903

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: 0.682 AC: 168397 AN: 246790 AF XY: 0.677

Gnomad AFR exome AF: 0.822

Gnomad AMR exome AF: 0.826

Gnomad ASJ exome AF: 0.644

Gnomad EAS exome AF: 0.908

Gnomad FIN exome AF: 0.591

Gnomad NFE exome AF: 0.573

Gnomad OTH exome AF: 0.655

GnomAD4 exome AF: 0.599 AC: 873685 AN: 1457414 Hom.: 268942 Cov.: 61 AF XY: 0.604 AC XY: 437885 AN XY: 724944

African (AFR) AF: 0.829 AC: 27681 AN: 33406

American (AMR) AF: 0.817 AC: 36536 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 16843 AN: 26108

East Asian (EAS) AF: 0.902 AC: 35787 AN: 39696

South Asian (SAS) AF: 0.786 AC: 67735 AN: 86140

European-Finnish (FIN) AF: 0.590 AC: 30489 AN: 51636

Middle Eastern (MID) AF: 0.720 AC: 3030 AN: 4206

European-Non Finnish (NFE) AF: 0.556 AC: 617858 AN: 1111344

Other (OTH) AF: 0.627 AC: 37726 AN: 60172

GnomAD4 genome AF: 0.680 AC: 103501 AN: 152246 Hom.: 36434 Cov.: 35 AF XY: 0.686 AC XY: 51050 AN XY: 74434

African (AFR) AF: 0.819 AC: 34061 AN: 41568

American (AMR) AF: 0.758 AC: 11595 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2175 AN: 3472

East Asian (EAS) AF: 0.903 AC: 4666 AN: 5170

South Asian (SAS) AF: 0.794 AC: 3838 AN: 4832

European-Finnish (FIN) AF: 0.606 AC: 6423 AN: 10606

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

European-Non Finnish (NFE) AF: 0.567 AC: 38554 AN: 67978

Other (OTH) AF: 0.692 AC: 1461 AN: 2112

Alfa AF: 0.622 Hom.: 12926

Bravo AF: 0.695

Asia WGS AF: 0.842 AC: 2923 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 10323412) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.96
PhyloP100		2.3
PromoterAI		-0.033	Neutral
Mutation Taster		=289/11	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: rs1801704; hg19: chr5-148206375;