NM_000674.3:c.622C>T

Variant names:

• chr1-203165541-C-T
• rs148415221
• NM_000674.3:c.622C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_000674.3(ADORA1):​c.622C>T​(p.Arg208Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000706 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000072 (0 hom.)
• Consequence: ADORA1 NM_000674.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.13
• Publications: 4 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12543085).
• BS2: High AC in GnomAd4 at 9 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	NM_000674.3	MANE Select	c.622C>T	p.Arg208Cys	missense	Exon 4 of 4	NP_000665.1	P30542-1
	ADORA1	NM_001048230.2		c.622C>T	p.Arg208Cys	missense	Exon 3 of 3	NP_001041695.1	P30542-1
	ADORA1	NM_001365065.1		c.418C>T	p.Arg140Cys	missense	Exon 3 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.622C>T	p.Arg208Cys	missense	Exon 4 of 4	ENSP00000338435.4	P30542-1
	ADORA1	ENST00000309502.7	TSL:1	c.622C>T	p.Arg208Cys	missense	Exon 6 of 6	ENSP00000308549.3	P30542-1
	ADORA1	ENST00000367236.8	TSL:1	c.622C>T	p.Arg208Cys	missense	Exon 3 of 3	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152194 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 34 AN: 251310 AF XY: 0.000103

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000718 AC: 105 AN: 1461594 Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42 AN XY: 727052

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000895 AC: 4 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 51 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000351 AC: 39 AN: 1111806

Other (OTH) AF: 0.000149 AC: 9 AN: 60380

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74476

African (AFR) AF: 0.0000241 AC: 1 AN: 41572

American (AMR) AF: 0.00 AC: 0 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000801 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.000140 AC: 17

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.1
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.29
Sift	Benign	0.18	T
Sift4G	Benign	0.095	T
Polyphen		0.73	P
Vest4		0.59
MVP		0.86
MPC		1.0
ClinPred		0.29	T
GERP RS		5.5
Varity_R		0.42
gMVP		0.67
Mutation Taster		=28/72	disease causing

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

Other links and lift over

dbSNP: rs148415221; hg19: chr1-203134669; COSMIC: COSV55141762; COSMIC: COSV55141762;