rs17852405

Variant names:

• chr1-203165701-C-A
• rs17852405
• NM_000674.3:c.782C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-203165701-C-A
• chr1-203165701-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000674.3(ADORA1):​c.782C>A​(p.Pro261Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADORA1 NM_000674.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01
• Publications: 7 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

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.782C>A	p.Pro261Gln	missense	Exon 4 of 4	NP_000665.1	P30542-1
	ADORA1	NM_001048230.2		c.782C>A	p.Pro261Gln	missense	Exon 3 of 3	NP_001041695.1	P30542-1
	ADORA1	NM_001365065.1		c.578C>A	p.Pro193Gln	missense	Exon 3 of 3	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.782C>A	p.Pro261Gln	missense	Exon 4 of 4	ENSP00000338435.4	P30542-1
	ADORA1	ENST00000309502.7	TSL:1	c.782C>A	p.Pro261Gln	missense	Exon 6 of 6	ENSP00000308549.3	P30542-1
	ADORA1	ENST00000367236.8	TSL:1	c.782C>A	p.Pro261Gln	missense	Exon 3 of 3	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.0
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.17
Sift	Benign	0.062	T
Sift4G	Benign	0.096	T
Polyphen		0.95	P
Vest4		0.64
MutPred		0.19		Loss of helix (P = 0.0626)
MVP		0.89
MPC		1.6
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.50
gMVP		0.67
Mutation Taster		=59/41	polymorphism

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: rs17852405; hg19: chr1-203134829;