1-203128847-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_000674.3(ADORA1):c.6G>A(p.Pro2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000887 in 1,594,848 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (4 hom.)
• Consequence: ADORA1 NM_000674.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.413

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

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 1-203128847-G-A is Benign according to our data. Variant chr1-203128847-G-A is described in ClinVar as [Benign]. Clinvar id is 716278.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.413 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00465 (708/152242) while in subpopulation AFR AF= 0.0161 (668/41538). AF 95% confidence interval is 0.0151. There are 11 homozygotes in gnomad4. There are 327 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 709 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA1	NM_000674.3	c.6G>A	p.Pro2=	synonymous_variant	3/4	ENST00000337894.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA1	ENST00000337894.9	c.6G>A	p.Pro2=	synonymous_variant	3/4	2	NM_000674.3	P1
ADORA1	ENST00000309502.7	c.6G>A	p.Pro2=	synonymous_variant	5/6	1		P1
ADORA1	ENST00000367236.8	c.6G>A	p.Pro2=	synonymous_variant	2/3	1		P1
ADORA1	ENST00000367235.1	c.6G>A	p.Pro2=	synonymous_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 709 AN: 152124 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00141 AC: 337 AN: 239210 Hom.: 2 AF XY: 0.00104 AC XY: 134 AN XY: 129334

Gnomad AFR exome AF: 0.0190

Gnomad AMR exome AF: 0.000703

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000696

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000181

Gnomad OTH exome AF: 0.000339

GnomAD4 exome AF: 0.000489 AC: 706 AN: 1442606 Hom.: 4 Cov.: 31 AF XY: 0.000440 AC XY: 315 AN XY: 716104

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.000768

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000107

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.00117

GnomAD4 genome AF: 0.00465 AC: 708 AN: 152242 Hom.: 11 Cov.: 32 AF XY: 0.00439 AC XY: 327 AN XY: 74426

Gnomad4 AFR AF: 0.0161

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00302 Hom.: 0

Bravo AF: 0.00603

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	14
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs61731145; hg19: chr1-203097975; COSMIC: COSV58808714; COSMIC: COSV58808714;