rs16851020

Variant names:

• chr1-203164524-G-T
• rs16851020
• NM_000674.3:c.342-737G>T

Variant summary

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

The NM_000674.3(ADORA1):​c.342-737G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,084 control chromosomes in the GnomAD database, including 4,345 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 0.21 (4345 hom., cov: 32)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 8 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA1	NM_000674.3	c.342-737G>T		intron_variant	Intron 3 of 3	ENST00000337894.9	NP_000665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADORA1	ENST00000337894.9	c.342-737G>T		intron_variant	Intron 3 of 3	2	NM_000674.3	ENSP00000338435.4

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31724 AN: 151966 Hom.: 4332 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.209 AC: 31772 AN: 152084 Hom.: 4345 Cov.: 32 AF XY: 0.206 AC XY: 15297 AN XY: 74332

African (AFR) AF: 0.388 AC: 16091 AN: 41430

American (AMR) AF: 0.248 AC: 3794 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.146 AC: 757 AN: 5180

South Asian (SAS) AF: 0.110 AC: 533 AN: 4824

European-Finnish (FIN) AF: 0.110 AC: 1170 AN: 10598

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8354 AN: 67984

Other (OTH) AF: 0.195 AC: 412 AN: 2110

Alfa AF: 0.158 Hom.: 2955

Bravo AF: 0.230

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.7
DANN	Benign	0.64
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs16851020; hg19: chr1-203133652;