rs12135643

Variant names:

• chr1-203131170-C-A
• rs12135643
• NM_000674.3:c.341+1988C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000674.3(ADORA1):​c.341+1988C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,204 control chromosomes in the GnomAD database, including 1,853 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 0.14 (1853 hom., cov: 33)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	NM_000674.3	MANE Select	c.341+1988C>A		intron	N/A	NP_000665.1	P30542-1
	ADORA1	NM_001048230.2		c.341+1988C>A		intron	N/A	NP_001041695.1	P30542-1
	ADORA1	NM_001365065.1		c.-69+1988C>A		intron	N/A	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.341+1988C>A		intron	N/A	ENSP00000338435.4	P30542-1
	ADORA1	ENST00000309502.7	TSL:1	c.341+1988C>A		intron	N/A	ENSP00000308549.3	P30542-1
	ADORA1	ENST00000367236.8	TSL:1	c.341+1988C>A		intron	N/A	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20578 AN: 152086 Hom.: 1851 Cov.: 33

Gnomad AFR AF: 0.0348

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20574 AN: 152204 Hom.: 1853 Cov.: 33 AF XY: 0.133 AC XY: 9917 AN XY: 74406

African (AFR) AF: 0.0347 AC: 1442 AN: 41562

American (AMR) AF: 0.135 AC: 2062 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 560 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0407 AC: 196 AN: 4816

European-Finnish (FIN) AF: 0.211 AC: 2233 AN: 10582

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13591 AN: 67988

Other (OTH) AF: 0.156 AC: 329 AN: 2108

Alfa AF: 0.154 Hom.: 1380

Bravo AF: 0.128

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-0.038
Mutation Taster		=100/0	polymorphism (auto)

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: rs12135643; hg19: chr1-203100298; COSMIC: COSV58809442; COSMIC: COSV58809442;