rs5760410

Variant names:

• chr22-24419438-G-A
• rs5760410
• ENST00000358654.2:n.*861+4694G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-24419438-G-A
• chr22-24419438-G-C
• chr22-24419438-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000358654.2(SPECC1L-ADORA2A):​n.*861+4694G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 150,744 control chromosomes in the GnomAD database, including 20,209 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 0.52 (20209 hom., cov: 31)
• Consequence: SPECC1L-ADORA2A ENST00000358654.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 16 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L-ADORA2A	NR_103546.1		n.3905+4694G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPECC1L-ADORA2A	ENST00000358654.2	TSL:2	n.*861+4694G>A		intron	N/A	ENSP00000351480.2	F8WAN1
	ADORA2A	ENST00000467385.5	TSL:4	n.381+1179G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.518 AC: 77991 AN: 150626 Hom.: 20166 Cov.: 31

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.498

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.518 AC: 78096 AN: 150744 Hom.: 20209 Cov.: 31 AF XY: 0.517 AC XY: 38133 AN XY: 73726

African (AFR) AF: 0.543 AC: 22435 AN: 41292

American (AMR) AF: 0.529 AC: 8045 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1627 AN: 3422

East Asian (EAS) AF: 0.551 AC: 2820 AN: 5116

South Asian (SAS) AF: 0.448 AC: 2112 AN: 4716

European-Finnish (FIN) AF: 0.498 AC: 5233 AN: 10518

Middle Eastern (MID) AF: 0.434 AC: 126 AN: 290

European-Non Finnish (NFE) AF: 0.510 AC: 34233 AN: 67174

Other (OTH) AF: 0.523 AC: 1095 AN: 2092

Alfa AF: 0.512 Hom.: 38802

Bravo AF: 0.523

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.29
DANN	Benign	0.20
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs5760410; hg19: chr22-24815406;