rs3753472

Variant names:

• chr1-203162405-T-C
• rs3753472
• NM_000674.3:c.342-2856T>C

Variant summary

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

The NM_000674.3(ADORA1):​c.342-2856T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,900 control chromosomes in the GnomAD database, including 5,670 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 0.25 (5670 hom., cov: 31)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.599
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	NM_000674.3	MANE Select	c.342-2856T>C		intron	N/A	NP_000665.1	P30542-1
	ADORA1	NM_001048230.2		c.342-2856T>C		intron	N/A	NP_001041695.1	P30542-1
	ADORA1	NM_001365065.1		c.-68-2651T>C		intron	N/A	NP_001351994.1	B7Z1L9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	ENST00000337894.9	TSL:2 MANE Select	c.342-2856T>C		intron	N/A	ENSP00000338435.4	P30542-1
	ADORA1	ENST00000309502.7	TSL:1	c.342-2856T>C		intron	N/A	ENSP00000308549.3	P30542-1
	ADORA1	ENST00000367236.8	TSL:1	c.342-2856T>C		intron	N/A	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37648 AN: 151782 Hom.: 5669 Cov.: 31

Gnomad AFR AF: 0.0899

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.248 AC: 37654 AN: 151900 Hom.: 5670 Cov.: 31 AF XY: 0.246 AC XY: 18264 AN XY: 74232

African (AFR) AF: 0.0899 AC: 3727 AN: 41454

American (AMR) AF: 0.198 AC: 3025 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3468

East Asian (EAS) AF: 0.0929 AC: 480 AN: 5168

South Asian (SAS) AF: 0.279 AC: 1340 AN: 4808

European-Finnish (FIN) AF: 0.377 AC: 3990 AN: 10570

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23424 AN: 67836

Other (OTH) AF: 0.237 AC: 500 AN: 2112

Alfa AF: 0.305 Hom.: 12373

Bravo AF: 0.225

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	8.5
DANN	Benign	0.71
PhyloP100		0.60
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: rs3753472; hg19: chr1-203131533;