rs11704959

Variant names:

• chr22-24424515-C-A
• rs11704959
• ENST00000358654.2:n.*862-8616C>A

Your query was ambiguous. Multiple possible variants found:

• chr22-24424515-C-A
• chr22-24424515-C-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.*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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA2A	NM_001278500.2	c.-275+887C>A		intron_variant	Intron 1 of 2		NP_001265429.1
SPECC1L-ADORA2A	NR_103546.1	n.3906-8616C>A		intron_variant	Intron 18 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPECC1L-ADORA2A	ENST00000358654.2	n.*862-8616C>A		intron_variant	Intron 18 of 19	2		ENSP00000351480.2

Frequencies

GnomAD3 genomes AF: 0.0722 AC: 10980 AN: 152050 Hom.: 483 Cov.: 32

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: 11 AN: 140 Hom.: 1 Cov.: 0 AF XY: 0.106 AC XY: 10 AN XY: 94

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.300 AC: 3 AN: 10

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0472 AC: 5 AN: 106

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0722 AC: 10981 AN: 152168 Hom.: 483 Cov.: 32 AF XY: 0.0722 AC XY: 5369 AN XY: 74406

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: 35 AN: 292

European-Non Finnish (NFE) AF: 0.0813 AC: 5523 AN: 67956

Other (OTH) AF: 0.0830 AC: 175 AN: 2108

Alfa AF: 0.0311 Hom.: 15

Bravo AF: 0.0764

Asia WGS AF: 0.0970 AC: 336 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.5
DANN	Benign	0.81
PhyloP100		-0.10
PromoterAI		0.058	Neutral
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

Other links and lift over

dbSNP: rs11704959; hg19: chr22-24820483;