Genetic Variant NM_000674.3:c.*646G>T (chr1-203166546-G-T) – 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.*646G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,462 control chromosomes in the GnomAD database, including 484 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 0.071 ( 483 hom., cov: 33)

Exomes 𝑓: 0.033 ( 1 hom. )

Consequence

ADORA1
NM_000674.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.273

Publications

8 publications found

Variant links:

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=-0.85).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA1	NM_000674.3 link	c.*646G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000337894.9	NP_000665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADORA1	ENST00000337894.9 link	c.*646G>T		3_prime_UTR_variant	Exon 4 of 4	2	NM_000674.3	ENSP00000338435.4

Frequencies

GnomAD3 genomes

AF:

0.0706

AC:

10735

AN:

152132

Hom.:

480

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0832

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0534

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.0906

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.0358

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.0593

GnomAD4 exome

AF:

0.0330

AC:

AN:

212

Hom.:

Cov.:

AF XY:

0.0197

AC XY:

AN XY:

152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.0455

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0316

AC:

AN:

158

Other (OTH)

AF:

0.0556

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0705

AC:

10740

AN:

152250

Hom.:

483

Cov.:

AF XY:

0.0712

AC XY:

5303

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0832

AC:

3455

AN:

41528

American (AMR)

AF:

0.0533

AC:

816

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0824

AC:

286

AN:

3472

East Asian (EAS)

AF:

0.0906

AC:

469

AN:

5178

South Asian (SAS)

AF:

0.200

AC:

965

AN:

4822

European-Finnish (FIN)

AF:

0.0358

AC:

380

AN:

10626

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0619

AC:

4208

AN:

67998

Other (OTH)

AF:

0.0592

AC:

125

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

513

1026

1540

2053

2566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0643

Hom.:

705

Bravo

AF:

0.0696

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.6

(source)

DANN

Benign

0.67

PhyloP100

0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over