rs9282641

Positions:

• chr3-122077921-G-A

Variant summary

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

The NM_006889.5(CD86):​c.-129G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 985,330 control chromosomes in the GnomAD database, including 3,529 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 0.070 (439 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3090 hom.)
• Consequence: CD86 NM_006889.5 5_prime_UTR
• Scores: Splicing: ADA: 0.00002264
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755

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]

CD86 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD86	NM_175862.5	c.15-13680G>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.15-13680G>A		intron_variant		1	NM_175862.5	ENSP00000332049.2

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10676 AN: 152112 Hom.: 438 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0769

GnomAD4 exome AF: 0.0846 AC: 70507 AN: 833100 Hom.: 3090 Cov.: 30 AF XY: 0.0849 AC XY: 32666 AN XY: 384734

Gnomad4 AFR exome AF: 0.0337

Gnomad4 AMR exome AF: 0.0650

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.000551

Gnomad4 SAS exome AF: 0.109

Gnomad4 FIN exome AF: 0.102

Gnomad4 NFE exome AF: 0.0855

Gnomad4 OTH exome AF: 0.0801

GnomAD4 genome AF: 0.0701 AC: 10673 AN: 152230 Hom.: 439 Cov.: 32 AF XY: 0.0710 AC XY: 5286 AN XY: 74416

Gnomad4 AFR AF: 0.0385

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.0868

Gnomad4 NFE AF: 0.0873

Gnomad4 OTH AF: 0.0756

Alfa AF: 0.0868 Hom.: 1321

Bravo AF: 0.0665

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0
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: rs9282641; hg19: chr3-121796768;