ENST00000798472.1:n.376+1168C>T

Variant names:

• chr5-148826465-C-T
• rs11959427
• ENST00000798472.1:n.376+1168C>T

Variant summary

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

The ENST00000798472.1(ENSG00000303969):​n.376+1168C>T variant causes a intron change. The variant allele was found at a frequency of 0.651 in 338,212 control chromosomes in the GnomAD database, including 74,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (36691 hom., cov: 33)
  • Exomes 𝑓: 0.63 (38161 hom.)
• Consequence: ENSG00000303969 ENST00000798472.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.64
• Publications: 30 publications found

Genes affected

ENSG00000303969 (HGNC:):

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 5-148826465-C-T is Benign according to our data. Variant chr5-148826465-C-T is described in ClinVar as Benign. ClinVar VariationId is 1259578.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6	c.-367C>T		upstream_gene_variant		ENST00000305988.6	NP_000015.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000303969	ENST00000798472.1	n.376+1168C>T		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1	n.349+1168C>T		intron_variant	Intron 3 of 4
ADRB2	ENST00000305988.6	c.-367C>T		upstream_gene_variant		6	NM_000024.6	ENSP00000305372.4

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103748 AN: 151994 Hom.: 36660 Cov.: 33

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.688

GnomAD4 exome AF: 0.625 AC: 116365 AN: 186100 Hom.: 38161 Cov.: 0 AF XY: 0.635 AC XY: 62263 AN XY: 98036

African (AFR) AF: 0.829 AC: 4239 AN: 5116

American (AMR) AF: 0.790 AC: 5032 AN: 6368

Ashkenazi Jewish (ASJ) AF: 0.632 AC: 3365 AN: 5322

East Asian (EAS) AF: 0.915 AC: 8222 AN: 8982

South Asian (SAS) AF: 0.783 AC: 18887 AN: 24120

European-Finnish (FIN) AF: 0.600 AC: 7235 AN: 12066

Middle Eastern (MID) AF: 0.704 AC: 583 AN: 828

European-Non Finnish (NFE) AF: 0.552 AC: 62114 AN: 112594

Other (OTH) AF: 0.625 AC: 6688 AN: 10704

GnomAD4 genome AF: 0.683 AC: 103840 AN: 152112 Hom.: 36691 Cov.: 33 AF XY: 0.689 AC XY: 51260 AN XY: 74352

African (AFR) AF: 0.820 AC: 34048 AN: 41522

American (AMR) AF: 0.759 AC: 11613 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2184 AN: 3470

East Asian (EAS) AF: 0.909 AC: 4663 AN: 5130

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

European-Finnish (FIN) AF: 0.632 AC: 6696 AN: 10590

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

European-Non Finnish (NFE) AF: 0.568 AC: 38601 AN: 67944

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

Alfa AF: 0.623 Hom.: 3799

Bravo AF: 0.696

Asia WGS AF: 0.845 AC: 2934 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.93
PhyloP100		3.6
PromoterAI		-0.084	Neutral

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: rs11959427; hg19: chr5-148206028;