rs548830344

Variant names:

• chr22-24419434-TAAGGGCCAAGCAGAAAAG-T
• rs548830344
• ENST00000358654.2:n.*861+4691_*861+4708delAAGGGCCAAGCAGAAAAG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The ENST00000358654.2(SPECC1L-ADORA2A):​n.*861+4691_*861+4708delAAGGGCCAAGCAGAAAAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00654 in 151,974 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0065 (3 hom., cov: 31)
• Consequence: SPECC1L-ADORA2A ENST00000358654.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.06

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 22-24419434-TAAGGGCCAAGCAGAAAAG-T is Benign according to our data. Variant chr22-24419434-TAAGGGCCAAGCAGAAAAG-T is described in ClinVar as [Benign]. Clinvar id is 1695039.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPECC1L-ADORA2A	NR_103546.1	n.3905+4701_3905+4718delCAGAAAAGAAGGGCCAAG		intron_variant	Intron 18 of 19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPECC1L-ADORA2A	ENST00000358654.2	n.*861+4691_*861+4708delAAGGGCCAAGCAGAAAAG		intron_variant	Intron 18 of 19	2		ENSP00000351480.2
ADORA2A	ENST00000467385.5	n.381+1176_381+1193delAAGGGCCAAGCAGAAAAG		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.00655 AC: 994 AN: 151856 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00511

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0146

Gnomad FIN AF: 0.00265

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00720

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

GnomAD4 genome AF: 0.00654 AC: 994 AN: 151974 Hom.: 3 Cov.: 31 AF XY: 0.00602 AC XY: 447 AN XY: 74296

Gnomad4 AFR AF: 0.00179

Gnomad4 AMR AF: 0.00510

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0146

Gnomad4 FIN AF: 0.00265

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00712

Alfa AF: 0.00686 Hom.: 1

Bravo AF: 0.00653

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SPECC1L: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs548830344; hg19: chr22-24815402;