chr1-203136227-G-A

Variant names:

• chr1-203136227-G-A
• rs3766566
• NM_000674.3:c.341+7045G>A

Variant summary

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

The NM_000674.3(ADORA1):​c.341+7045G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,096 control chromosomes in the GnomAD database, including 3,241 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 0.20 (3241 hom., cov: 32)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000674.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	NM_000674.3	MANE Select	c.341+7045G>A		intron	N/A	NP_000665.1
	ADORA1	NM_001048230.2		c.341+7045G>A		intron	N/A	NP_001041695.1
	ADORA1	NM_001365065.1		c.-69+7045G>A		intron	N/A	NP_001351994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	ENST00000337894.9	TSL:2 MANE Select	c.341+7045G>A		intron	N/A	ENSP00000338435.4
	ADORA1	ENST00000309502.7	TSL:1	c.341+7045G>A		intron	N/A	ENSP00000308549.3
	ADORA1	ENST00000367236.8	TSL:1	c.341+7045G>A		intron	N/A	ENSP00000356205.4

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29857 AN: 151978 Hom.: 3243 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.196 AC: 29844 AN: 152096 Hom.: 3241 Cov.: 32 AF XY: 0.197 AC XY: 14676 AN XY: 74326

African (AFR) AF: 0.106 AC: 4405 AN: 41518

American (AMR) AF: 0.262 AC: 3995 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3468

East Asian (EAS) AF: 0.327 AC: 1687 AN: 5158

South Asian (SAS) AF: 0.114 AC: 551 AN: 4826

European-Finnish (FIN) AF: 0.255 AC: 2694 AN: 10550

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15294 AN: 67984

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.203 Hom.: 3181

Bravo AF: 0.196

Asia WGS AF: 0.202 AC: 701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.30
DANN	Benign	0.42
PhyloP100		-3.4
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: rs3766566; hg19: chr1-203105355;