ENST00000358654.2:n.*862-8616C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000358654.2(SPECC1L-ADORA2A):n.*862-8616C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0722 in 152,308 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 0.072 ( 483 hom., cov: 32)

Exomes 𝑓: 0.079 ( 1 hom. )

Consequence

SPECC1L-ADORA2A
ENST00000358654.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.105

Publications

4 publications found

Variant links:

Genes affected

SPECC1L-ADORA2A (HGNC:49185): (SPECC1L-ADORA2A readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) genes on chromosome 22. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD) and is unlikely to produce a protein product. [provided by RefSeq, Jun 2013]

SPECC1L-ADORA2A links:

ADORA2A (HGNC:263): (adenosine A2a receptor) This gene encodes a member of the guanine nucleotide-binding protein (G protein)-coupled receptor (GPCR) superfamily, which is subdivided into classes and subtypes. The receptors are seven-pass transmembrane proteins that respond to extracellular cues and activate intracellular signal transduction pathways. This protein, an adenosine receptor of A2A subtype, uses adenosine as the preferred endogenous agonist and preferentially interacts with the G(s) and G(olf) family of G proteins to increase intracellular cAMP levels. It plays an important role in many biological functions, such as cardiac rhythm and circulation, cerebral and renal blood flow, immune function, pain regulation, and sleep. It has been implicated in pathophysiological conditions such as inflammatory diseases and neurodegenerative disorders. Alternative splicing results in multiple transcript variants. A read-through transcript composed of the upstream SPECC1L (sperm antigen with calponin homology and coiled-coil domains 1-like) and ADORA2A (adenosine A2a receptor) gene sequence has been identified, but it is thought to be non-coding. [provided by RefSeq, Jun 2013]

ADORA2A links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000358654.2. 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
	ADORA2A	NM_001278500.2		c.-275+887C>A		intron	N/A	NP_001265429.1
	SPECC1L-ADORA2A	NR_103546.1		n.3906-8616C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*862-8616C>A	intron	N/A	ENSP00000351480.2
ADORA2A	ENST00000444262.6	TSL:5	c.-316C>A	5_prime_UTR	Exon 1 of 3	ENSP00000414802.2
ADORA2A	ENST00000464977.5	TSL:4	c.-422C>A	5_prime_UTR	Exon 1 of 3	ENSP00000474895.1

Frequencies

GnomAD3 genomes

AF:

0.0722

AC:

10980

AN:

152050

Hom.:

483

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0413

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0799

Gnomad EAS

AF:

0.0534

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0274

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0813

Gnomad OTH

AF:

0.0844

GnomAD4 exome

AF:

0.0786

AC:

AN:

140

Hom.:

Cov.:

AF XY:

0.106

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.300

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0472

AC:

AN:

106

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0722

AC:

10981

AN:

152168

Hom.:

483

Cov.:

AF XY:

0.0722

AC XY:

5369

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0412

AC:

1713

AN:

41546

American (AMR)

AF:

0.125

AC:

1915

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0799

AC:

277

AN:

3468

East Asian (EAS)

AF:

0.0533

AC:

274

AN:

5136

South Asian (SAS)

AF:

0.138

AC:

667

AN:

4830

European-Finnish (FIN)

AF:

0.0274

AC:

291

AN:

10622

Middle Eastern (MID)

AF:

0.120

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0813

AC:

5523

AN:

67956

Other (OTH)

AF:

0.0830

AC:

175

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

502

1004

1506

2008

2510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

252

378

504

630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0311

Hom.:

Bravo

AF:

0.0764

Asia WGS

AF:

0.0970

AC:

336

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.5

(source)

DANN

Benign

0.81

PhyloP100

-0.10

PromoterAI

0.058

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over