rs2228079

chr1-203129147-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000674.3(ADORA1):c.306T>G(p.Ala102=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 1,613,614 control chromosomes in the GnomAD database, including 84,762 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 0.26 (6012 hom., cov: 32)
  • Exomes 𝑓: 0.32 (78750 hom.)
• Consequence: ADORA1 NM_000674.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.95

Genes affected

ADORA1 (HGNC:262): (adenosine A1 receptor) The protein encoded by this gene is an adenosine receptor that belongs to the G-protein coupled receptor 1 family. There are 3 types of adenosine receptors, each with a specific pattern of ligand binding and tissue distribution, and together they regulate a diverse set of physiologic functions. The type A1 receptors inhibit adenylyl cyclase, and play a role in the fertilization process. Animal studies also suggest a role for A1 receptors in kidney function and ethanol intoxication. Transcript variants with alternative splicing in the 5' UTR have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-3.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA1	NM_000674.3	c.306T>G	p.Ala102=	synonymous_variant	3/4	ENST00000337894.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA1	ENST00000337894.9	c.306T>G	p.Ala102=	synonymous_variant	3/4	2	NM_000674.3	P1
ADORA1	ENST00000309502.7	c.306T>G	p.Ala102=	synonymous_variant	5/6	1		P1
ADORA1	ENST00000367236.8	c.306T>G	p.Ala102=	synonymous_variant	2/3	1		P1
ADORA1	ENST00000367235.1	c.306T>G	p.Ala102=	synonymous_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39814 AN: 152018 Hom.: 6008 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.257

GnomAD3 exomes AF: 0.306 AC: 76837 AN: 250778 Hom.: 12676 AF XY: 0.317 AC XY: 43013 AN XY: 135490

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.149

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.300

GnomAD4 exome AF: 0.323 AC: 472360 AN: 1461478 Hom.: 78750 Cov.: 49 AF XY: 0.327 AC XY: 237740 AN XY: 727006

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.258

Gnomad4 EAS exome AF: 0.144

Gnomad4 SAS exome AF: 0.409

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.332

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.262 AC: 39831 AN: 152136 Hom.: 6012 Cov.: 32 AF XY: 0.263 AC XY: 19535 AN XY: 74380

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.257

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.255

Alfa AF: 0.298 Hom.: 3167

Bravo AF: 0.248

Asia WGS AF: 0.259 AC: 900 AN: 3478

EpiCase AF: 0.331

EpiControl AF: 0.323

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	1.1
Dann	Benign	0.47

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: rs2228079; hg19: chr1-203098275; COSMIC: COSV58809382; COSMIC: COSV58809382;