rs3766553

Variant names:

• chr1-203163914-A-G
• rs3766553
• NM_000674.3:c.342-1347A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000674.3(ADORA1):​c.342-1347A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,038 control chromosomes in the GnomAD database, including 19,581 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 0.50 (19581 hom., cov: 32)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA1	NM_000674.3	c.342-1347A>G		intron_variant	Intron 3 of 3	ENST00000337894.9	NP_000665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADORA1	ENST00000337894.9	c.342-1347A>G		intron_variant	Intron 3 of 3	2	NM_000674.3	ENSP00000338435.4

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75986 AN: 151920 Hom.: 19553 Cov.: 32

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.474

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.500 AC: 76064 AN: 152038 Hom.: 19581 Cov.: 32 AF XY: 0.495 AC XY: 36749 AN XY: 74314

African (AFR) AF: 0.609 AC: 25247 AN: 41478

American (AMR) AF: 0.462 AC: 7055 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3468

East Asian (EAS) AF: 0.243 AC: 1258 AN: 5170

South Asian (SAS) AF: 0.423 AC: 2039 AN: 4826

European-Finnish (FIN) AF: 0.490 AC: 5175 AN: 10566

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.477 AC: 32402 AN: 67928

Other (OTH) AF: 0.469 AC: 989 AN: 2110

Alfa AF: 0.479 Hom.: 10361

Bravo AF: 0.501

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.7
DANN	Benign	0.48
PhyloP100		0.068
Mutation Taster		=100/0	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: rs3766553; hg19: chr1-203133042;