rs4308217

chr3-122074340-C-Achr3-122074340-C-T

Variant summary

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

The NM_175862.5(CD86):c.15-17261C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,138 control chromosomes in the GnomAD database, including 6,352 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 0.26 (6352 hom., cov: 31)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD86	NM_175862.5	c.15-17261C>A		intron_variant		ENST00000330540.7
CD86	NM_001206924.2	c.15-17261C>A		intron_variant
CD86	NM_001206925.2	c.-183+18837C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.15-17261C>A		intron_variant		1	NM_175862.5	A2
CD86	ENST00000469710.5	c.-183+18837C>A		intron_variant		2
CD86	ENST00000493101.5	c.15-17261C>A		intron_variant		2
CD86	ENST00000478390.1	n.128-17261C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38839 AN: 152020 Hom.: 6343 Cov.: 31

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.255 AC: 38847 AN: 152138 Hom.: 6352 Cov.: 31 AF XY: 0.256 AC XY: 19006 AN XY: 74378

Gnomad4 AFR AF: 0.0736

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.283

Alfa AF: 0.313 Hom.: 11057

Bravo AF: 0.262

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.24
Dann	Benign	0.43

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: rs4308217; hg19: chr3-121793187;