1-203133600-A-G

Variant names:

• chr1-203133600-A-G
• rs6701725
• NM_000674.3:c.341+4418A>G

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+4418A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,098 control chromosomes in the GnomAD database, including 29,053 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 0.61 (29053 hom., cov: 32)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 11 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	NM_000674.3	MANE Select	c.341+4418A>G		intron	N/A	NP_000665.1
	ADORA1	NM_001048230.2		c.341+4418A>G		intron	N/A	NP_001041695.1
	ADORA1	NM_001365065.1		c.-69+4418A>G		intron	N/A	NP_001351994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA1	ENST00000337894.9	TSL:2 MANE Select	c.341+4418A>G		intron	N/A	ENSP00000338435.4
	ADORA1	ENST00000309502.7	TSL:1	c.341+4418A>G		intron	N/A	ENSP00000308549.3
	ADORA1	ENST00000367236.8	TSL:1	c.341+4418A>G		intron	N/A	ENSP00000356205.4

Frequencies

GnomAD3 genomes AF: 0.614 AC: 93384 AN: 151980 Hom.: 29041 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.614 AC: 93423 AN: 152098 Hom.: 29053 Cov.: 32 AF XY: 0.616 AC XY: 45796 AN XY: 74334

African (AFR) AF: 0.596 AC: 24709 AN: 41464

American (AMR) AF: 0.712 AC: 10892 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.519 AC: 1800 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4016 AN: 5162

South Asian (SAS) AF: 0.591 AC: 2852 AN: 4828

European-Finnish (FIN) AF: 0.619 AC: 6555 AN: 10584

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40760 AN: 67974

Other (OTH) AF: 0.614 AC: 1298 AN: 2114

Alfa AF: 0.609 Hom.: 115162

Bravo AF: 0.625

Asia WGS AF: 0.687 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		-0.26
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: rs6701725; hg19: chr1-203102728;