chr17-15972621-A-G

Variant names:

• chr17-15972621-A-G
• rs2779211
• NM_000676.4:c.336-2058A>G

Variant summary

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

The NM_000676.4(ADORA2B):​c.336-2058A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,994 control chromosomes in the GnomAD database, including 15,466 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 0.43 (15466 hom., cov: 31)
• Consequence: ADORA2B NM_000676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 13 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.528 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.336-2058A>G		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.336-2058A>G		intron	N/A	ENSP00000304501.2

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64914 AN: 151876 Hom.: 15459 Cov.: 31

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.427 AC: 64944 AN: 151994 Hom.: 15466 Cov.: 31 AF XY: 0.426 AC XY: 31648 AN XY: 74266

African (AFR) AF: 0.231 AC: 9588 AN: 41448

American (AMR) AF: 0.447 AC: 6823 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2217 AN: 3466

East Asian (EAS) AF: 0.145 AC: 747 AN: 5168

South Asian (SAS) AF: 0.385 AC: 1855 AN: 4812

European-Finnish (FIN) AF: 0.562 AC: 5936 AN: 10554

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36174 AN: 67958

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.380 Hom.: 1765

Bravo AF: 0.409

Asia WGS AF: 0.308 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.4
DANN	Benign	0.83
PhyloP100		0.35
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: rs2779211; hg19: chr17-15875935; COSMIC: COSV58481765; COSMIC: COSV58481765;