rs2041458

Positions:

• chr17-15957524-A-C
• chr17-15957524-A-G
• chr17-15957524-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000676.4(ADORA2B):​c.335+11941A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,112 control chromosomes in the GnomAD database, including 56,921 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 0.83 (56921 hom., cov: 30)
• Consequence: ADORA2B NM_000676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.875

Genes affected

ADORA2B (HGNC:264): (adenosine A2b receptor) This gene encodes an adenosine receptor that is a member of the G protein-coupled receptor superfamily. This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with netrin-1, which is involved in axon elongation. The gene is located near the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA2B	NM_000676.4	c.335+11941A>C		intron_variant		ENST00000304222.3	NP_000667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA2B	ENST00000304222.3	c.335+11941A>C		intron_variant		1	NM_000676.4	ENSP00000304501	P1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126430 AN: 151994 Hom.: 56915 Cov.: 30

Gnomad AFR AF: 0.451

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.870

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

GnomAD4 genome AF: 0.831 AC: 126454 AN: 152112 Hom.: 56921 Cov.: 30 AF XY: 0.835 AC XY: 62115 AN XY: 74366

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.896

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.982

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.992

Gnomad4 OTH AF: 0.871

Alfa AF: 0.802 Hom.: 5700

Bravo AF: 0.810

Asia WGS AF: 0.938 AC: 3260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.54

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

Other links and lift over

dbSNP: rs2041458; hg19: chr17-15860838;