rs56298433

Variant names:

• chr1-203128110-G-T
• rs56298433
• NM_000674.3:c.-212-168G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000674.3(ADORA1):​c.-212-168G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0122 in 152,288 control chromosomes in the GnomAD database, including 33 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 0.012 (33 hom., cov: 32)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 1 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]

ADORA1-AS2 (HGNC:40066):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0122 (1857/152288) while in subpopulation AFR AF = 0.0385 (1600/41562). AF 95% confidence interval is 0.0369. There are 33 homozygotes in GnomAd4. There are 940 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1857 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.-212-168G>T		intron	N/A	NP_000665.1	P30542-1
	ADORA1	NM_001048230.2		c.-58+182G>T		intron	N/A	NP_001041695.1	P30542-1
	ADORA1	NM_001365065.1		c.-467+182G>T		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.-212-168G>T		intron	N/A	ENSP00000338435.4	P30542-1
	ADORA1	ENST00000309502.7	TSL:1	c.-212-168G>T		intron	N/A	ENSP00000308549.3	P30542-1
	ADORA1	ENST00000367236.8	TSL:1	c.-58+182G>T		intron	N/A	ENSP00000356205.4	P30542-1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1857 AN: 152170 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.0386

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00616

Gnomad SAS AF: 0.0299

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00958

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

GnomAD4 genome AF: 0.0122 AC: 1857 AN: 152288 Hom.: 33 Cov.: 32 AF XY: 0.0126 AC XY: 940 AN XY: 74456

African (AFR) AF: 0.0385 AC: 1600 AN: 41562

American (AMR) AF: 0.00222 AC: 34 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00618 AC: 32 AN: 5180

South Asian (SAS) AF: 0.0297 AC: 143 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 67998

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.00867 Hom.: 2

Bravo AF: 0.0133

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.94
PhyloP100		1.0
PromoterAI		-0.064	Neutral
Mutation Taster		=100/0	polymorphism

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: rs56298433; hg19: chr1-203097238;