17-15951633-A-G

Variant names:

• chr17-15951633-A-G
• rs758858
• NM_000676.4:c.335+6050A>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.335+6050A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.895 in 152,288 control chromosomes in the GnomAD database, including 62,490 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 0.89 (62490 hom., cov: 34)
• Consequence: ADORA2B NM_000676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA2B	NM_000676.4	c.335+6050A>G		intron_variant	Intron 1 of 1	ENST00000304222.3	NP_000667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADORA2B	ENST00000304222.3	c.335+6050A>G		intron_variant	Intron 1 of 1	1	NM_000676.4	ENSP00000304501.2

Frequencies

GnomAD3 genomes AF: 0.895 AC: 136195 AN: 152170 Hom.: 62456 Cov.: 34

Gnomad AFR AF: 0.670

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.982

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.918

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

GnomAD4 genome AF: 0.895 AC: 136277 AN: 152288 Hom.: 62490 Cov.: 34 AF XY: 0.897 AC XY: 66825 AN XY: 74458

African (AFR) AF: 0.670 AC: 27821 AN: 41526

American (AMR) AF: 0.922 AC: 14113 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3395 AN: 3472

East Asian (EAS) AF: 0.975 AC: 5051 AN: 5180

South Asian (SAS) AF: 0.982 AC: 4745 AN: 4832

European-Finnish (FIN) AF: 0.984 AC: 10465 AN: 10630

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67547 AN: 68024

Other (OTH) AF: 0.919 AC: 1945 AN: 2116

Alfa AF: 0.953 Hom.: 48114

Bravo AF: 0.882

Asia WGS AF: 0.958 AC: 3330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.23
DANN	Benign	0.66
PhyloP100		-2.0
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: rs758858; hg19: chr17-15854947;