rs2681416

Positions:

• chr3-122098766-G-A

Variant summary

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

The NM_175862.5(CD86):​c.65-4746G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,116 control chromosomes in the GnomAD database, including 5,317 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 0.26 (5317 hom., cov: 32)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.973

Genes affected

CD86 (HGNC:1705): (CD86 molecule) This gene encodes a type I membrane protein that is a member of the immunoglobulin superfamily. This protein is expressed by antigen-presenting cells, and it is the ligand for two proteins at the cell surface of T cells, CD28 antigen and cytotoxic T-lymphocyte-associated protein 4. Binding of this protein with CD28 antigen is a costimulatory signal for activation of the T-cell. Binding of this protein with cytotoxic T-lymphocyte-associated protein 4 negatively regulates T-cell activation and diminishes the immune response. Alternative splicing results in several transcript variants encoding different isoforms.[provided by RefSeq, May 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD86	NM_175862.5	c.65-4746G>A		intron_variant		ENST00000330540.7	NP_787058.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7	c.65-4746G>A		intron_variant		1	NM_175862.5	ENSP00000332049.2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38816 AN: 151998 Hom.: 5314 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.255 AC: 38845 AN: 152116 Hom.: 5317 Cov.: 32 AF XY: 0.251 AC XY: 18646 AN XY: 74348

Gnomad4 AFR AF: 0.174

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.139

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.247

Alfa AF: 0.295 Hom.: 2249

Bravo AF: 0.249

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.69

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: rs2681416; hg19: chr3-121817613;