rs2681411

Positions:

• chr3-122066784-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.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

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=-0.84).
• 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/exons	MANE	Protein	UniProt
CD86	NM_175862.5	c.14+11281G>A		intron_variant		ENST00000330540.7	NP_787058.5
CD86	NM_001206924.2	c.14+11281G>A		intron_variant			NP_001193853.2
CD86	NM_001206925.2	c.-183+11281G>A		intron_variant			NP_001193854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7	c.14+11281G>A		intron_variant		1	NM_175862.5	ENSP00000332049	A2
CD86	ENST00000469710.5	c.-183+11281G>A		intron_variant		2		ENSP00000418988
CD86	ENST00000493101.5	c.14+11281G>A		intron_variant		2		ENSP00000420230
CD86	ENST00000478390.1	n.127+11281G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.594

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.565

Gnomad4 FIN AF: 0.596

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.557

Alfa AF: 0.599 Hom.: 36007

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

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: rs2681411; hg19: chr3-121785631;