chr1-203129327-T-C

Variant names:

• chr1-203129327-T-C
• rs10920569
• NM_000674.3:c.341+145T>C

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+145T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 1,430,822 control chromosomes in the GnomAD database, including 74,794 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 0.26 (5944 hom., cov: 33)
  • Exomes 𝑓: 0.32 (68850 hom.)
• Consequence: ADORA1 NM_000674.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA1	NM_000674.3	c.341+145T>C		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.341+145T>C		intron_variant	Intron 3 of 3	2	NM_000674.3	ENSP00000338435.4
ADORA1	ENST00000309502.7	c.341+145T>C		intron_variant	Intron 5 of 5	1		ENSP00000308549.3
ADORA1	ENST00000367236.8	c.341+145T>C		intron_variant	Intron 2 of 2	1		ENSP00000356205.4
ADORA1	ENST00000367235.1	c.341+145T>C		intron_variant	Intron 2 of 2	2		ENSP00000356204.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39193 AN: 152076 Hom.: 5941 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.323 AC: 413194 AN: 1278628 Hom.: 68850 AF XY: 0.326 AC XY: 202998 AN XY: 621946

African (AFR) AF: 0.0971 AC: 2731 AN: 28140

American (AMR) AF: 0.284 AC: 5850 AN: 20614

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 4896 AN: 18906

East Asian (EAS) AF: 0.145 AC: 5053 AN: 34882

South Asian (SAS) AF: 0.410 AC: 25986 AN: 63314

European-Finnish (FIN) AF: 0.337 AC: 10449 AN: 30970

Middle Eastern (MID) AF: 0.265 AC: 1282 AN: 4838

European-Non Finnish (NFE) AF: 0.333 AC: 340780 AN: 1023546

Other (OTH) AF: 0.303 AC: 16167 AN: 53418

GnomAD4 genome AF: 0.258 AC: 39207 AN: 152194 Hom.: 5944 Cov.: 33 AF XY: 0.259 AC XY: 19248 AN XY: 74394

African (AFR) AF: 0.110 AC: 4550 AN: 41538

American (AMR) AF: 0.263 AC: 4029 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 892 AN: 3472

East Asian (EAS) AF: 0.150 AC: 776 AN: 5182

South Asian (SAS) AF: 0.393 AC: 1891 AN: 4816

European-Finnish (FIN) AF: 0.337 AC: 3566 AN: 10590

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.333 AC: 22644 AN: 67984

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.318 Hom.: 4411

Bravo AF: 0.243

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.70
PhyloP100		-0.041
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: rs10920569; hg19: chr1-203098455;