1-203129147-T-A

Variant names:

• chr1-203129147-T-A
• NM_000674.3:c.306T>A
• ADORA1 p.Ala102Ala

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000674.3(ADORA1):​c.306T>A​(p.Ala102Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A102A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADORA1 NM_000674.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.95
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-3.95 with no splicing effect.

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.306T>A	p.Ala102Ala	synonymous	Exon 3 of 4	NP_000665.1	P30542-1
	ADORA1	NM_001048230.2		c.306T>A	p.Ala102Ala	synonymous	Exon 2 of 3	NP_001041695.1	P30542-1
	ADORA1	NM_001365065.1		c.-104T>A		5_prime_UTR	Exon 2 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.306T>A	p.Ala102Ala	synonymous	Exon 3 of 4	ENSP00000338435.4	P30542-1
	ADORA1	ENST00000309502.7	TSL:1	c.306T>A	p.Ala102Ala	synonymous	Exon 5 of 6	ENSP00000308549.3	P30542-1
	ADORA1	ENST00000367236.8	TSL:1	c.306T>A	p.Ala102Ala	synonymous	Exon 2 of 3	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.98
DANN	Benign	0.68
PhyloP100		-4.0
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-203098275;