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

Variant names:

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

Variant summary

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

The ENST00000798472.1(ENSG00000303969):​n.376+1168C>A variant causes a intron change. The variant was absent in control chromosomes in GnomAD project. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000303969 ENST00000798472.1 intron
• Clinical Significance: Not reported in ClinVar
• 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: 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=-0.68).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 186894 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 98448

African (AFR) AF: 0.00 AC: 0 AN: 5126

American (AMR) AF: 0.00 AC: 0 AN: 6382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5348

East Asian (EAS) AF: 0.00 AC: 0 AN: 8992

South Asian (SAS) AF: 0.00 AC: 0 AN: 24174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 834

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 113162

Other (OTH) AF: 0.00 AC: 0 AN: 10760

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	11
DANN	Benign	0.89
PhyloP100		3.6
PromoterAI		-0.097	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;