5-148828099-C-T

Variant names:

• chr5-148828099-C-T
• rs28763957
• NM_000024.6:c.*26C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000024.6(ADRB2):​c.*26C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,181,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: ADRB2 NM_000024.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRB2	NM_000024.6	c.*26C>T		3_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.*26C>T		3_prime_UTR_variant	Exon 1 of 1	6	NM_000024.6	ENSP00000305372.4
ENSG00000303969	ENST00000798472.1	n.376+2802C>T		intron_variant	Intron 3 of 4
ENSG00000303969	ENST00000798473.1	n.349+2802C>T		intron_variant	Intron 3 of 4

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 8.46e-7 AC: 1 AN: 1181542 Hom.: 0 Cov.: 25 AF XY: 0.00000169 AC XY: 1 AN XY: 592428

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28442

American (AMR) AF: 0.00 AC: 0 AN: 32608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20358

East Asian (EAS) AF: 0.00 AC: 0 AN: 37870

South Asian (SAS) AF: 0.00 AC: 0 AN: 70870

European-Finnish (FIN) AF: 0.0000200 AC: 1 AN: 50116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4948

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 885698

Other (OTH) AF: 0.00 AC: 0 AN: 50632

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 27

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.0
DANN	Benign	0.55
PhyloP100		-0.17

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: rs28763957; hg19: chr5-148207662;