Variant chr1-111500517-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_000677.4(ADORA3):c.390C>T(p.Ala130=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,614,170 control chromosomes in the GnomAD database, including 366 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 0.019 ( 27 hom., cov: 32)

Exomes 𝑓: 0.018 ( 339 hom. )

Consequence

ADORA3
NM_000677.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.961

Variant links:

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]

ADORA3 links:

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]

TMIGD3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP7

Synonymous conserved (PhyloP=-0.961 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0187 (2843/152296) while in subpopulation AFR AF= 0.0249 (1035/41536). AF 95% confidence interval is 0.0237. There are 27 homozygotes in gnomad4. There are 1307 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA3	NM_000677.4 linkuse as main transcript	c.390C>T	p.Ala130=	synonymous_variant	2/2	ENST00000241356.5	NP_000668.1
TMIGD3	NM_020683.7 linkuse as main transcript	c.350+2488C>T		intron_variant		ENST00000369716.9	NP_065734.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA3	ENST00000241356.5 linkuse as main transcript	c.390C>T	p.Ala130=	synonymous_variant	2/2	1	NM_000677.4	ENSP00000241356	P1	P0DMS8-1
TMIGD3	ENST00000369716.9 linkuse as main transcript	c.350+2488C>T		intron_variant		1	NM_020683.7	ENSP00000358730	P1	P0DMS9-2

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2842

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.00999

Gnomad SAS

AF:

0.0226

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0191

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0170

AC:

4229

AN:

249210

Hom.:

AF XY:

0.0177

AC XY:

2382

AN XY:

134928

show subpopulations

Gnomad AFR exome

AF:

0.0264

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.00549

Gnomad SAS exome

AF:

0.0281

Gnomad FIN exome

AF:

0.00287

Gnomad NFE exome

AF:

0.0193

Gnomad OTH exome

AF:

0.0167

GnomAD4 exome

AF:

0.0180

AC:

26328

AN:

1461874

Hom.:

339

Cov.:

AF XY:

0.0183

AC XY:

13306

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0251

Gnomad4 AMR exome

AF:

0.0112

Gnomad4 ASJ exome

AF:

0.0141

Gnomad4 EAS exome

AF:

0.0149

Gnomad4 SAS exome

AF:

0.0262

Gnomad4 FIN exome

AF:

0.00281

Gnomad4 NFE exome

AF:

0.0183

Gnomad4 OTH exome

AF:

0.0177

GnomAD4 genome

AF:

0.0187

AC:

2843

AN:

152296

Hom.:

Cov.:

AF XY:

0.0175

AC XY:

1307

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.0112

Gnomad4 EAS

AF:

0.0102

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0223

Alfa

AF:

0.0194

Hom.:

Bravo

AF:

0.0201

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0230

EpiControl

AF:

0.0228

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.8

DANN

Benign

0.64

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over