5-148826364-G-C

Variant names:

• chr5-148826364-G-C
• rs11168070
• ENST00000798472.1:n.376+1067G>C

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+1067G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 190,996 control chromosomes in the GnomAD database, including 44,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.68 (36683 hom., cov: 32)
  • Exomes 𝑓: 0.62 (7919 hom.)
• Consequence: ENSG00000303969 ENST00000798472.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210
• Publications: 28 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=-0.84).
• BP6: Variant 5-148826364-G-C is Benign according to our data. Variant chr5-148826364-G-C is described in ClinVar as Benign. ClinVar VariationId is 1235095.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000798472.1. 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.-468G>C		upstream_gene	N/A	NP_000015.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000303969	ENST00000798472.1		n.376+1067G>C		intron	N/A
	ENSG00000303969	ENST00000798473.1		n.349+1067G>C		intron	N/A
	ADRB2	ENST00000305988.6	TSL:6 MANE Select	c.-468G>C		upstream_gene	N/A	ENSP00000305372.4

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103737 AN: 151960 Hom.: 36653 Cov.: 32

Gnomad AFR AF: 0.821

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.910

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.690

GnomAD4 exome AF: 0.616 AC: 23991 AN: 38918 Hom.: 7919 Cov.: 0 AF XY: 0.630 AC XY: 12679 AN XY: 20110

African (AFR) AF: 0.833 AC: 443 AN: 532

American (AMR) AF: 0.797 AC: 2394 AN: 3002

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 473 AN: 772

East Asian (EAS) AF: 0.901 AC: 1276 AN: 1416

South Asian (SAS) AF: 0.776 AC: 4378 AN: 5640

European-Finnish (FIN) AF: 0.592 AC: 1133 AN: 1914

Middle Eastern (MID) AF: 0.680 AC: 83 AN: 122

European-Non Finnish (NFE) AF: 0.537 AC: 12619 AN: 23512

Other (OTH) AF: 0.594 AC: 1192 AN: 2008

GnomAD4 genome AF: 0.683 AC: 103828 AN: 152078 Hom.: 36683 Cov.: 32 AF XY: 0.690 AC XY: 51257 AN XY: 74338

African (AFR) AF: 0.820 AC: 34043 AN: 41504

American (AMR) AF: 0.758 AC: 11597 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2183 AN: 3466

East Asian (EAS) AF: 0.910 AC: 4665 AN: 5128

South Asian (SAS) AF: 0.795 AC: 3830 AN: 4820

European-Finnish (FIN) AF: 0.633 AC: 6701 AN: 10584

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

European-Non Finnish (NFE) AF: 0.568 AC: 38615 AN: 67970

Other (OTH) AF: 0.695 AC: 1467 AN: 2110

Alfa AF: 0.623 Hom.: 3800

Bravo AF: 0.696

Asia WGS AF: 0.844 AC: 2929 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.2
DANN	Benign	0.46
PhyloP100		0.021
PromoterAI		-0.017	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11168070; hg19: chr5-148205927; COSMIC: COSV60006366;