3-122102296-T-G

Variant names:

• chr3-122102296-T-G
• rs2332096
• NM_175862.5:c.65-1216T>G

Variant summary

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

The NM_175862.5(CD86):​c.65-1216T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,688 control chromosomes in the GnomAD database, including 20,201 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 0.51 (20201 hom., cov: 29)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 12 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 (AMR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD86	NM_175862.5	c.65-1216T>G		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.65-1216T>G		intron_variant	Intron 2 of 6	1	NM_175862.5	ENSP00000332049.2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77016 AN: 151570 Hom.: 20178 Cov.: 29

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.508 AC: 77068 AN: 151688 Hom.: 20201 Cov.: 29 AF XY: 0.511 AC XY: 37837 AN XY: 74092

African (AFR) AF: 0.391 AC: 16169 AN: 41326

American (AMR) AF: 0.643 AC: 9784 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1911 AN: 3470

East Asian (EAS) AF: 0.316 AC: 1629 AN: 5162

South Asian (SAS) AF: 0.566 AC: 2720 AN: 4802

European-Finnish (FIN) AF: 0.558 AC: 5855 AN: 10500

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.548 AC: 37206 AN: 67894

Other (OTH) AF: 0.550 AC: 1159 AN: 2108

Alfa AF: 0.528 Hom.: 15035

Bravo AF: 0.508

Asia WGS AF: 0.502 AC: 1747 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	4.1
DANN	Benign	0.66
PhyloP100		0.094
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: rs2332096; hg19: chr3-121821143;