rs3792285

Variant names:

• chr3-122100739-C-A
• rs3792285
• NM_175862.5:c.65-2773C>A

Variant summary

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

The NM_175862.5(CD86):​c.65-2773C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,152 control chromosomes in the GnomAD database, including 864 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 0.10 (864 hom., cov: 31)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD86	NM_175862.5	c.65-2773C>A		intron_variant	Intron 2 of 6	ENST00000330540.7	NP_787058.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7	c.65-2773C>A		intron_variant	Intron 2 of 6	1	NM_175862.5	ENSP00000332049.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15766 AN: 152034 Hom.: 864 Cov.: 31

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.0836

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0602

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.104 AC: 15786 AN: 152152 Hom.: 864 Cov.: 31 AF XY: 0.102 AC XY: 7624 AN XY: 74418

African (AFR) AF: 0.0921 AC: 3821 AN: 41504

American (AMR) AF: 0.0834 AC: 1275 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3468

East Asian (EAS) AF: 0.112 AC: 578 AN: 5164

South Asian (SAS) AF: 0.107 AC: 514 AN: 4820

European-Finnish (FIN) AF: 0.0602 AC: 639 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8012 AN: 67982

Other (OTH) AF: 0.104 AC: 220 AN: 2112

Alfa AF: 0.112 Hom.: 1665

Bravo AF: 0.105

Asia WGS AF: 0.0830 AC: 288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.57
DANN	Benign	0.59
PhyloP100		-0.28
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: rs3792285; hg19: chr3-121819586; COSMIC: COSV107273933;