1-203165293-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_000674.3(ADORA1):c.374C>T(p.Ala125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000955 in 1,571,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

ADORA1
NM_000674.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.27

Publications

3 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09702048).

BP6

Variant 1-203165293-C-T is Benign according to our data. Variant chr1-203165293-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 1086093.

BS2

High AC in GnomAd4 at 21 AD gene.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ADORA1	NM_000674.3	MANE Select	c.374C>T	p.Ala125Val	missense	Exon 4 of 4	NP_000665.1	P30542-1
ADORA1	NM_001048230.2		c.374C>T	p.Ala125Val	missense	Exon 3 of 3	NP_001041695.1	P30542-1
ADORA1	NM_001365065.1		c.170C>T	p.Ala57Val	missense	Exon 3 of 3	NP_001351994.1	B7Z1L9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADORA1	ENST00000337894.9	TSL:2 MANE Select	c.374C>T	p.Ala125Val	missense	Exon 4 of 4	ENSP00000338435.4	P30542-1
ADORA1	ENST00000309502.7	TSL:1	c.374C>T	p.Ala125Val	missense	Exon 6 of 6	ENSP00000308549.3	P30542-1
ADORA1	ENST00000367236.8	TSL:1	c.374C>T	p.Ala125Val	missense	Exon 3 of 3	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000608

AC:

AN:

213896

AF XY:

0.0000611

show subpopulations

Gnomad AFR exome

AF:

0.000191

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000908

Gnomad OTH exome

AF:

0.000197

GnomAD4 exome

AF:

0.0000909

AC:

129

AN:

1419046

Hom.:

Cov.:

AF XY:

0.0000698

AC XY:

AN XY:

701618

show subpopulations

African (AFR)

AF:

0.0000933

AC:

AN:

32138

American (AMR)

AF:

0.00

AC:

AN:

39052

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23140

East Asian (EAS)

AF:

0.00

AC:

AN:

39290

South Asian (SAS)

AF:

0.00

AC:

AN:

78956

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.000113

AC:

123

AN:

1090702

Other (OTH)

AF:

0.0000514

AC:

AN:

58378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.000138

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41424

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.0000742

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.27

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.68

M_CAP

Benign

0.0061

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

1.3

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

REVEL

Benign

0.054

Sift

Benign

0.50

Sift4G

Benign

0.51

Polyphen

0.0010

Vest4

0.073

MVP

0.57

MPC

0.70

ClinPred

0.018

GERP RS

2.8

Varity_R

0.11

gMVP

0.69

Mutation Taster

=90/10

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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