5-148827884-G-C

Variant names:

• chr5-148827884-G-C
• rs1042719
• NM_000024.6:c.1053G>C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_000024.6(ADRB2):​c.1053G>C​(p.Gly351Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,613,788 control chromosomes in the GnomAD database, including 75,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (8075 hom., cov: 32)
  • Exomes 𝑓: 0.30 (67444 hom.)
• Consequence: ADRB2 NM_000024.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.960
• Publications: 59 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 5-148827884-G-C is Benign according to our data. Variant chr5-148827884-G-C is described in ClinVar as Benign. ClinVar VariationId is 1236780.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.96 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6	c.1053G>C	p.Gly351Gly	synonymous_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.1053G>C	p.Gly351Gly	synonymous_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4
ENSG00000303969	ENST00000798472.1	n.376+2587G>C		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1	n.349+2587G>C		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48756 AN: 151880 Hom.: 8074 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.337

GnomAD2 exomes AF: 0.337 AC: 84643 AN: 251332 AF XY: 0.336

Gnomad AFR exome AF: 0.349

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.296

Gnomad EAS exome AF: 0.446

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.290

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.299 AC: 436760 AN: 1461790 Hom.: 67444 Cov.: 54 AF XY: 0.302 AC XY: 219398 AN XY: 727186

African (AFR) AF: 0.353 AC: 11832 AN: 33476

American (AMR) AF: 0.436 AC: 19491 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 7768 AN: 26134

East Asian (EAS) AF: 0.482 AC: 19150 AN: 39696

South Asian (SAS) AF: 0.390 AC: 33676 AN: 86256

European-Finnish (FIN) AF: 0.258 AC: 13807 AN: 53418

Middle Eastern (MID) AF: 0.370 AC: 2135 AN: 5768

European-Non Finnish (NFE) AF: 0.279 AC: 310173 AN: 1111930

Other (OTH) AF: 0.310 AC: 18728 AN: 60392

GnomAD4 genome AF: 0.321 AC: 48780 AN: 151998 Hom.: 8075 Cov.: 32 AF XY: 0.321 AC XY: 23877 AN XY: 74282

African (AFR) AF: 0.348 AC: 14432 AN: 41430

American (AMR) AF: 0.382 AC: 5831 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3464

East Asian (EAS) AF: 0.452 AC: 2336 AN: 5166

South Asian (SAS) AF: 0.400 AC: 1927 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2826 AN: 10556

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19305 AN: 67972

Other (OTH) AF: 0.335 AC: 707 AN: 2108

Alfa AF: 0.296 Hom.: 2335

Bravo AF: 0.329

Asia WGS AF: 0.417 AC: 1450 AN: 3478

EpiCase AF: 0.293

EpiControl AF: 0.302

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	7.6
DANN	Benign	0.80
PhyloP100		0.96
Mutation Taster		=99/1	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: rs1042719; hg19: chr5-148207447; COSMIC: COSV60005218;