rs9831894

chr3-122081640-A-C

Variant summary

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

The NM_175862.5(CD86):c.15-9961A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,156 control chromosomes in the GnomAD database, including 9,434 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 0.32 (9434 hom., cov: 32)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD86	NM_175862.5	c.15-9961A>C		intron_variant		ENST00000330540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.15-9961A>C		intron_variant		1	NM_175862.5	A2

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48487 AN: 152038 Hom.: 9417 Cov.: 32

Gnomad AFR AF: 0.0991

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.319 AC: 48509 AN: 152156 Hom.: 9434 Cov.: 32 AF XY: 0.321 AC XY: 23883 AN XY: 74376

Gnomad4 AFR AF: 0.0989

Gnomad4 AMR AF: 0.493

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.357

Alfa AF: 0.381 Hom.: 18837

Bravo AF: 0.317

Asia WGS AF: 0.320 AC: 1110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.7
Dann	Benign	0.75

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: rs9831894; hg19: chr3-121800487;