1-203129147-T-G

Variant names:

• chr1-203129147-T-G
• rs2228079
• NM_000674.3:c.306T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000674.3(ADORA1):​c.306T>G​(p.Ala102Ala) 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
• Publications: 33 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ADORA1	NM_000674.3	c.306T>G	p.Ala102Ala	synonymous_variant	Exon 3 of 4	ENST00000337894.9	NP_000665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADORA1	ENST00000337894.9	c.306T>G	p.Ala102Ala	synonymous_variant	Exon 3 of 4	2	NM_000674.3	ENSP00000338435.4
ADORA1	ENST00000309502.7	c.306T>G	p.Ala102Ala	synonymous_variant	Exon 5 of 6	1		ENSP00000308549.3
ADORA1	ENST00000367236.8	c.306T>G	p.Ala102Ala	synonymous_variant	Exon 2 of 3	1		ENSP00000356205.4
ADORA1	ENST00000367235.1	c.306T>G	p.Ala102Ala	synonymous_variant	Exon 2 of 3	2		ENSP00000356204.1

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

GnomAD2 exomes AF: 0.306 AC: 76837 AN: 250778 AF XY: 0.317

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 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

African (AFR) AF: 0.116 AC: 3881 AN: 33476

American (AMR) AF: 0.295 AC: 13194 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 6740 AN: 26100

East Asian (EAS) AF: 0.144 AC: 5712 AN: 39694

South Asian (SAS) AF: 0.409 AC: 35299 AN: 86204

European-Finnish (FIN) AF: 0.338 AC: 18028 AN: 53394

Middle Eastern (MID) AF: 0.262 AC: 1511 AN: 5768

European-Non Finnish (NFE) AF: 0.332 AC: 369635 AN: 1111778

Other (OTH) AF: 0.304 AC: 18360 AN: 60370

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

African (AFR) AF: 0.125 AC: 5178 AN: 41520

American (AMR) AF: 0.264 AC: 4038 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3472

East Asian (EAS) AF: 0.148 AC: 765 AN: 5178

South Asian (SAS) AF: 0.392 AC: 1888 AN: 4818

European-Finnish (FIN) AF: 0.337 AC: 3564 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.333 AC: 22644 AN: 67974

Other (OTH) AF: 0.255 AC: 537 AN: 2110

Alfa AF: 0.293 Hom.: 4228

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
PhyloP100		-4.0
Mutation Taster		=99/1	polymorphism (auto)

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