NM_175862.5:c.553G>T

Variant names:

• chr3-122106350-G-T
• rs2681417
• NM_175862.5:c.553G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_175862.5(CD86):​c.553G>T​(p.Val185Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD86 NM_175862.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14466748).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175862.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD86	NM_175862.5	MANE Select	c.553G>T	p.Val185Phe	missense	Exon 4 of 7	NP_787058.5
	CD86	NM_006889.5		c.535G>T	p.Val179Phe	missense	Exon 4 of 7	NP_008820.4	P42081-3
	CD86	NM_176892.2		c.535G>T	p.Val179Phe	missense	Exon 4 of 6	NP_795711.2	P42081-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD86	ENST00000330540.7	TSL:1 MANE Select	c.553G>T	p.Val185Phe	missense	Exon 4 of 7	ENSP00000332049.2	P42081-1
	CD86	ENST00000393627.6	TSL:1	c.535G>T	p.Val179Phe	missense	Exon 4 of 7	ENSP00000377248.2	P42081-3
	CD86	ENST00000478741.1	TSL:5	c.538G>T	p.Val180Phe	missense	Exon 3 of 5	ENSP00000417195.1	H7C4F8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.094
Sift	Benign	0.21	T
Sift4G	Benign	0.18	T
Polyphen		0.91	P
Vest4		0.21
MutPred		0.28		Gain of glycosylation at Y182 (P = 0.0015)
MVP		0.32
MPC		1.0
ClinPred		0.49	T
GERP RS		-1.9
Varity_R		0.17
gMVP		0.27
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2681417; hg19: chr3-121825197;