17-15966243-G-T

Variant names:

• chr17-15966243-G-T
• rs17715109
• NM_000676.4:c.336-8436G>T

Variant summary

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

The NM_000676.4(ADORA2B):​c.336-8436G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 152,296 control chromosomes in the GnomAD database, including 205 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 0.050 (205 hom., cov: 33)
• Consequence: ADORA2B NM_000676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000676.4. 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
	ADORA2B	NM_000676.4	MANE Select	c.336-8436G>T		intron	N/A	NP_000667.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA2B	ENST00000304222.3	TSL:1 MANE Select	c.336-8436G>T		intron	N/A	ENSP00000304501.2

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7573 AN: 152178 Hom.: 204 Cov.: 33

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.0282

Gnomad EAS AF: 0.0743

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.0439

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0370

Gnomad OTH AF: 0.0531

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

GnomAD4 genome AF: 0.0498 AC: 7586 AN: 152296 Hom.: 205 Cov.: 33 AF XY: 0.0506 AC XY: 3766 AN XY: 74464

African (AFR) AF: 0.0724 AC: 3007 AN: 41550

American (AMR) AF: 0.0458 AC: 701 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0282 AC: 98 AN: 3470

East Asian (EAS) AF: 0.0745 AC: 386 AN: 5180

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4828

European-Finnish (FIN) AF: 0.0439 AC: 466 AN: 10612

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0370 AC: 2517 AN: 68034

Other (OTH) AF: 0.0520 AC: 110 AN: 2114

Alfa AF: 0.0477 Hom.: 60

Bravo AF: 0.0512

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.55
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

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: rs17715109; hg19: chr17-15869557;