rs34923252

Positions:

• chr22-24442384-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_028484.3(ADORA2A-AS1):​n.685-244A>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 152,878 control chromosomes in the GnomAD database, including 81 homozygotes. 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: 𝑓 0.010 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: ADORA2A-AS1 NR_028484.3 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

Genes affected

ADORA2A-AS1 (HGNC:37122): (ADORA2A antisense RNA 1)

ADORA2A (HGNC:263): (adenosine A2a receptor) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily, which is subdivided into classes and subtypes. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein, an adenosine receptor of A2A subtype, uses adenosine as the preferred endogenous agonist and preferentially interacts with the G(s) and G(olf) family of G proteins to increase intracellular cAMP levels. It plays an important role in many biological functions, such as cardiac rhythm and circulation, cerebral and renal blood flow, immune function, pain regulation, and sleep. It has been implicated in pathophysiological conditions such as inflammatory diseases and neurodegenerative disorders. Alternative splicing results in multiple transcript variants. A read-through transcript composed of the upstream SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding. [provided by RefSeq, Jun 2013]

SPECC1L-ADORA2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA2A-AS1	NR_028484.3	n.685-244A>T		intron_variant, non_coding_transcript_variant
ADORA2A	NM_000675.6			downstream_gene_variant		ENST00000337539.12	NP_000666.2
SPECC1L-ADORA2A	NR_103546.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA2A-AS1	ENST00000326341.8	n.411-244A>T		intron_variant, non_coding_transcript_variant		5
ADORA2A	ENST00000337539.12			downstream_gene_variant		1	NM_000675.6	ENSP00000336630	P1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1570 AN: 152202 Hom.: 80 Cov.: 33

Gnomad AFR AF: 0.00953

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0861

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00179 AC: 1 AN: 558 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 326

Gnomad4 EAS exome AF: 0.00714

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0103 AC: 1574 AN: 152320 Hom.: 81 Cov.: 33 AF XY: 0.0124 AC XY: 926 AN XY: 74480

Gnomad4 AFR AF: 0.00952

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0869

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.000985

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00603 Hom.: 2

Bravo AF: 0.00822

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.75

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs34923252; hg19: chr22-24838352;