Variant chr5-148826812-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.29

Variant links:

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]

ADRB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 link	c.-20C>T		5_prime_UTR_variant	Exon 1 of 1	ENST00000305988.6	NP_000015.2	P07550X5DQM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRB2	ENST00000305988 link	c.-20C>T		5_prime_UTR_variant	Exon 1 of 1		NM_000024.6	ENSP00000305372.4		P07550

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

103410

AN:

152130

Hom.:

36403

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.682

AC:

168397

AN:

246790

Hom.:

59626

AF XY:

0.677

AC XY:

90584

AN XY:

133742

show subpopulations

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 SAS exome

AF:

0.789

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.:

AF XY:

0.604

AC XY:

437885

AN XY:

724944

show subpopulations

Gnomad4 AFR exome

AF:

0.829

Gnomad4 AMR exome

AF:

0.817

Gnomad4 ASJ exome

AF:

0.645

Gnomad4 EAS exome

AF:

0.902

Gnomad4 SAS exome

AF:

0.786

Gnomad4 FIN exome

AF:

0.590

Gnomad4 NFE exome

AF:

0.556

Gnomad4 OTH exome

AF:

0.627

GnomAD4 genome

AF:

0.680

AC:

103501

AN:

152246

Hom.:

36434

Cov.:

AF XY:

0.686

AC XY:

51050

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.819

Gnomad4 AMR

AF:

0.758

Gnomad4 ASJ

AF:

0.626

Gnomad4 EAS

AF:

0.903

Gnomad4 SAS

AF:

0.794

Gnomad4 FIN

AF:

0.606

Gnomad4 NFE

AF:

0.567

Gnomad4 OTH

AF:

0.692

Alfa

AF:

0.618

Hom.:

8574

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

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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

DANN

Benign

0.96

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over