1-203166546-G-T

Position:

• chr1-203166546-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000674.3(ADORA1):​c.*646G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 152,462 control chromosomes in the GnomAD database, including 484 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 0.071 (483 hom., cov: 33)
  • Exomes 𝑓: 0.033 (1 hom.)
• Consequence: ADORA1 NM_000674.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.273

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA1	NM_000674.3	c.*646G>T		3_prime_UTR_variant	4/4	ENST00000337894.9	NP_000665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA1	ENST00000337894.9	c.*646G>T		3_prime_UTR_variant	4/4	2	NM_000674.3	ENSP00000338435	P1

Frequencies

GnomAD3 genomes AF: 0.0706 AC: 10735 AN: 152132 Hom.: 480 Cov.: 33

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0906

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0330 AC: 7 AN: 212 Hom.: 1 Cov.: 0 AF XY: 0.0197 AC XY: 3 AN XY: 152

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0455

Gnomad4 NFE exome AF: 0.0316

Gnomad4 OTH exome AF: 0.0556

GnomAD4 genome AF: 0.0705 AC: 10740 AN: 152250 Hom.: 483 Cov.: 33 AF XY: 0.0712 AC XY: 5303 AN XY: 74436

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.0906

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.0358

Gnomad4 NFE AF: 0.0619

Gnomad4 OTH AF: 0.0592

Alfa AF: 0.0624 Hom.: 505

Bravo AF: 0.0696

Asia WGS AF: 0.117 AC: 407 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs12744240; hg19: chr1-203135674;