chr17-15958018-C-T

Variant names:

• chr17-15958018-C-T
• rs2535611
• NM_000676.4:c.335+12435C>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.335+12435C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 148,694 control chromosomes in the GnomAD database, including 68,670 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 0.96 (68670 hom., cov: 27)
• Consequence: ADORA2B NM_000676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.72
• Publications: 14 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=-1.06).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADORA2B	NM_000676.4	c.335+12435C>T		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+12435C>T		intron_variant	Intron 1 of 1	1	NM_000676.4	ENSP00000304501.2

Frequencies

GnomAD3 genomes AF: 0.961 AC: 142806 AN: 148622 Hom.: 68642 Cov.: 27

Gnomad AFR AF: 0.906

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.970

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.969

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

GnomAD4 genome AF: 0.961 AC: 142870 AN: 148694 Hom.: 68670 Cov.: 27 AF XY: 0.959 AC XY: 69327 AN XY: 72278

African (AFR) AF: 0.906 AC: 36531 AN: 40320

American (AMR) AF: 0.942 AC: 14166 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.970 AC: 3350 AN: 3452

East Asian (EAS) AF: 0.973 AC: 4968 AN: 5104

South Asian (SAS) AF: 0.978 AC: 4643 AN: 4748

European-Finnish (FIN) AF: 0.979 AC: 9246 AN: 9442

Middle Eastern (MID) AF: 0.966 AC: 280 AN: 290

European-Non Finnish (NFE) AF: 0.992 AC: 66781 AN: 67336

Other (OTH) AF: 0.969 AC: 1997 AN: 2060

Alfa AF: 0.951 Hom.: 13236

Asia WGS AF: 0.900 AC: 2994 AN: 3324

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.10
DANN	Benign	0.52
PhyloP100		-2.7
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: rs2535611; hg19: chr17-15861332; COSMIC: COSV58483389;