rs2681411

Variant names:

• chr3-122066784-G-A
• rs2681411
• NM_175862.5:c.14+11281G>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.14+11281G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,824 control chromosomes in the GnomAD database, including 22,204 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 0.53 (22204 hom., cov: 31)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 14 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 = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD86	NM_175862.5	c.14+11281G>A		intron_variant	Intron 1 of 6	ENST00000330540.7	NP_787058.5
CD86	NM_001206925.2	c.-183+11281G>A		intron_variant	Intron 1 of 5		NP_001193854.2
CD86	NM_001206924.2	c.14+11281G>A		intron_variant	Intron 1 of 5		NP_001193853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7	c.14+11281G>A		intron_variant	Intron 1 of 6	1	NM_175862.5	ENSP00000332049.2
CD86	ENST00000469710.5	c.-183+11281G>A		intron_variant	Intron 1 of 5	2		ENSP00000418988.1
CD86	ENST00000493101.5	c.14+11281G>A		intron_variant	Intron 1 of 5	2		ENSP00000420230.1
CD86	ENST00000478390.1	n.127+11281G>A		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79928 AN: 151706 Hom.: 22190 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.594

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.566

Gnomad FIN AF: 0.596

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.527 AC: 79970 AN: 151824 Hom.: 22204 Cov.: 31 AF XY: 0.529 AC XY: 39203 AN XY: 74176

African (AFR) AF: 0.349 AC: 14416 AN: 41356

American (AMR) AF: 0.672 AC: 10251 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.594 AC: 2062 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1683 AN: 5154

South Asian (SAS) AF: 0.565 AC: 2711 AN: 4794

European-Finnish (FIN) AF: 0.596 AC: 6283 AN: 10548

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40714 AN: 67942

Other (OTH) AF: 0.557 AC: 1173 AN: 2106

Alfa AF: 0.593 Hom.: 48123

Bravo AF: 0.523

Asia WGS AF: 0.497 AC: 1728 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	5.8
DANN	Benign	0.48
PhyloP100		0.15
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: rs2681411; hg19: chr3-121785631;