dbSNP rs4950926: ADORA1:c.*1638G>A (chr1-203167538-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000674.3(ADORA1):c.*1638G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,128 control chromosomes in the GnomAD database, including 7,596 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 0.28 ( 7575 hom., cov: 30)

Exomes 𝑓: 0.38 ( 21 hom. )

Consequence

ADORA1
NM_000674.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.405

Publications

3 publications found

Variant links:

COSMIC-nc: COSV55144327

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]

ADORA1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADORA1	NM_000674.3	MANE Select	c.*1638G>A	downstream_gene	N/A	NP_000665.1
ADORA1	NM_001048230.2		c.*1638G>A	downstream_gene	N/A	NP_001041695.1
ADORA1	NM_001365065.1		c.*1638G>A	downstream_gene	N/A	NP_001351994.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ADORA1	ENST00000337894.9	TSL:2 MANE Select	c.*1638G>A	downstream_gene	N/A	ENSP00000338435.4
ADORA1	ENST00000309502.7	TSL:1	c.*1638G>A	downstream_gene	N/A	ENSP00000308549.3
ADORA1	ENST00000367236.8	TSL:1	c.*1638G>A	downstream_gene	N/A	ENSP00000356205.4

Frequencies

GnomAD3 genomes

AF:

0.282

AC:

42757

AN:

151762

Hom.:

7572

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0884

Gnomad AMI

AF:

0.642

Gnomad AMR

AF:

0.259

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.0259

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.403

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.306

GnomAD4 exome

AF:

0.383

AC:

AN:

248

Hom.:

AF XY:

0.390

AC XY:

AN XY:

172

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.250

AC:

AN:

European-Finnish (FIN)

AF:

0.419

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.396

AC:

AN:

154

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.282

AC:

42761

AN:

151880

Hom.:

7575

Cov.:

AF XY:

0.281

AC XY:

20855

AN XY:

74214

show subpopulations

African (AFR)

AF:

0.0884

AC:

3663

AN:

41432

American (AMR)

AF:

0.258

AC:

3949

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1264

AN:

3464

East Asian (EAS)

AF:

0.0260

AC:

134

AN:

5158

South Asian (SAS)

AF:

0.214

AC:

1029

AN:

4816

European-Finnish (FIN)

AF:

0.403

AC:

4248

AN:

10532

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27145

AN:

67884

Other (OTH)

AF:

0.302

AC:

637

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1391

2782

4172

5563

6954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

430

860

1290

1720

2150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.297

Hom.:

1115

Bravo

AF:

0.264

Asia WGS

AF:

0.109

AC:

383

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.41

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over