rs2229155

Variant names:

• chr1-111500010-A-G
• rs2229155
• NM_000677.4:c.897T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-111500010-A-G
• chr1-111500010-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_000677.4(ADORA3):​c.897T>C​(p.Ala299Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.812 in 1,613,974 control chromosomes in the GnomAD database, including 532,628 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 0.80 (48432 hom., cov: 32)
  • Exomes 𝑓: 0.81 (484196 hom.)
• Consequence: ADORA3 NM_000677.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 27 publications found

Genes affected

ADORA3 (HGNC:268): (adenosine A3 receptor) This gene encodes a protein that belongs to the family of adenosine receptors, which are G-protein-coupled receptors that are involved in a variety of intracellular signaling pathways and physiological functions. The receptor encoded by this gene mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death. Alternative splicing results in multiple transcript variants. This gene shares its 5' terminal exon with some transcripts from overlapping GeneID:57413, which encodes an immunoglobulin domain-containing protein. [provided by RefSeq, Nov 2014]

TMIGD3 (HGNC:51375): (transmembrane and immunoglobulin domain containing 3) This gene encodes a transmembrane and immunoglobulin domain-containing protein. Alternative splicing results in multiple transcript variants, one of which shares its 5' terminal exon with that of the overlapping adenosine A3 receptor gene (GeneID:140), thus resulting in a fusion product. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=2.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000677.4. 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
	ADORA3	NM_000677.4	MANE Select	c.897T>C	p.Ala299Ala	synonymous	Exon 2 of 2	NP_000668.1
	TMIGD3	NM_020683.7	MANE Select	c.350+2995T>C		intron	N/A	NP_065734.5
	ADORA3	NM_001302679.2		c.462T>C	p.Ala154Ala	synonymous	Exon 2 of 2	NP_001289608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA3	ENST00000241356.5	TSL:1 MANE Select	c.897T>C	p.Ala299Ala	synonymous	Exon 2 of 2	ENSP00000241356.4
	TMIGD3	ENST00000369716.9	TSL:1 MANE Select	c.350+2995T>C		intron	N/A	ENSP00000358730.4
	TMIGD3	ENST00000369717.8	TSL:1	c.108-9248T>C		intron	N/A	ENSP00000358731.4

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121307 AN: 152098 Hom.: 48393 Cov.: 32

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.808

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.821

GnomAD2 exomes AF: 0.809 AC: 203480 AN: 251384 AF XY: 0.810

Gnomad AFR exome AF: 0.739

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.847

Gnomad EAS exome AF: 0.766

Gnomad FIN exome AF: 0.842

Gnomad NFE exome AF: 0.816

Gnomad OTH exome AF: 0.824

GnomAD4 exome AF: 0.813 AC: 1188637 AN: 1461758 Hom.: 484196 Cov.: 57 AF XY: 0.812 AC XY: 590362 AN XY: 727186

African (AFR) AF: 0.744 AC: 24910 AN: 33476

American (AMR) AF: 0.848 AC: 37923 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 22223 AN: 26128

East Asian (EAS) AF: 0.782 AC: 31024 AN: 39694

South Asian (SAS) AF: 0.770 AC: 66409 AN: 86250

European-Finnish (FIN) AF: 0.841 AC: 44914 AN: 53420

Middle Eastern (MID) AF: 0.894 AC: 5154 AN: 5768

European-Non Finnish (NFE) AF: 0.816 AC: 906952 AN: 1111906

Other (OTH) AF: 0.813 AC: 49128 AN: 60394

GnomAD4 genome AF: 0.798 AC: 121402 AN: 152216 Hom.: 48432 Cov.: 32 AF XY: 0.798 AC XY: 59410 AN XY: 74440

African (AFR) AF: 0.748 AC: 31052 AN: 41514

American (AMR) AF: 0.842 AC: 12889 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2953 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3998 AN: 5184

South Asian (SAS) AF: 0.764 AC: 3683 AN: 4822

European-Finnish (FIN) AF: 0.850 AC: 9005 AN: 10598

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55091 AN: 68010

Other (OTH) AF: 0.822 AC: 1735 AN: 2110

Alfa AF: 0.806 Hom.: 227393

Bravo AF: 0.799

Asia WGS AF: 0.770 AC: 2682 AN: 3478

EpiCase AF: 0.817

EpiControl AF: 0.827

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.3
DANN	Benign	0.48
PhyloP100		2.1

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: rs2229155; hg19: chr1-112042632; COSMIC: COSV108059968; COSMIC: COSV108059968;