rs6805035

chr3-122084301-A-Cchr3-122084301-A-G

Variant summary

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

The NM_175862.5(CD86):c.15-7300A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,140 control chromosomes in the GnomAD database, including 1,176 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 0.12 (1176 hom., cov: 32)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD86	NM_175862.5	c.15-7300A>C		intron_variant		ENST00000330540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.15-7300A>C		intron_variant		1	NM_175862.5	A2

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18311 AN: 152022 Hom.: 1175 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0855

Gnomad ASJ AF: 0.0639

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0503

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.120 AC: 18316 AN: 152140 Hom.: 1176 Cov.: 32 AF XY: 0.118 AC XY: 8761 AN XY: 74370

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.0639

Gnomad4 EAS AF: 0.00830

Gnomad4 SAS AF: 0.0504

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.104

Alfa AF: 0.130 Hom.: 151

Bravo AF: 0.118

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.3
Dann	Benign	0.54

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: rs6805035; hg19: chr3-121803148;