rs5996696

chr22-24431654-A-C

Variant summary

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

The NM_000675.6(ADORA2A):c.-274-1477A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0811 in 380,228 control chromosomes in the GnomAD database, including 3,097 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 0.11 (2217 hom., cov: 32)
  • Exomes 𝑓: 0.059 (880 hom.)
• Consequence: ADORA2A NM_000675.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51

Genes affected

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]

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

SPECC1L-ADORA2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA2A	NM_000675.6	c.-274-1477A>C		intron_variant		ENST00000337539.12
ADORA2A-AS1	NR_028484.3	n.1007-92T>G		intron_variant, non_coding_transcript_variant
SPECC1L-ADORA2A	NR_103546.1	n.3906-1477A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA2A	ENST00000337539.12	c.-274-1477A>C		intron_variant		1	NM_000675.6	P1
ADORA2A-AS1	ENST00000326341.8	n.733-92T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17304 AN: 152034 Hom.: 2207 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0624

Gnomad ASJ AF: 0.0325

Gnomad EAS AF: 0.0896

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0251

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0265

Gnomad OTH AF: 0.0946

GnomAD4 exome AF: 0.0590 AC: 13467 AN: 228076 Hom.: 880 Cov.: 0 AF XY: 0.0647 AC XY: 8202 AN XY: 126844

Gnomad4 AFR exome AF: 0.309

Gnomad4 AMR exome AF: 0.0323

Gnomad4 ASJ exome AF: 0.0402

Gnomad4 EAS exome AF: 0.0962

Gnomad4 SAS exome AF: 0.126

Gnomad4 FIN exome AF: 0.0236

Gnomad4 NFE exome AF: 0.0259

Gnomad4 OTH exome AF: 0.0540

GnomAD4 genome AF: 0.114 AC: 17361 AN: 152152 Hom.: 2217 Cov.: 32 AF XY: 0.114 AC XY: 8450 AN XY: 74394

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.0623

Gnomad4 ASJ AF: 0.0325

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0251

Gnomad4 NFE AF: 0.0266

Gnomad4 OTH AF: 0.0946

Alfa AF: 0.0604 Hom.: 332

Bravo AF: 0.124

Asia WGS AF: 0.126 AC: 436 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.28
Dann	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs5996696; hg19: chr22-24827622;