chr3-122106350-G-C

Variant names:

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

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>C​(p.Val185Leu) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V185F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CD86 NM_175862.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 42 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=0.08086097).

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>C	p.Val185Leu	missense	Exon 4 of 7	NP_787058.5
	CD86	NM_006889.5		c.535G>C	p.Val179Leu	missense	Exon 4 of 7	NP_008820.4	P42081-3
	CD86	NM_176892.2		c.535G>C	p.Val179Leu	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>C	p.Val185Leu	missense	Exon 4 of 7	ENSP00000332049.2	P42081-1
	CD86	ENST00000393627.6	TSL:1	c.535G>C	p.Val179Leu	missense	Exon 4 of 7	ENSP00000377248.2	P42081-3
	CD86	ENST00000478741.1	TSL:5	c.538G>C	p.Val180Leu	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	0.12
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.2
DANN	Benign	0.88
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.048
Sift	Benign	0.44	T
Sift4G	Benign	0.22	T
Polyphen		0.37	B
Vest4		0.047
MutPred		0.29		Gain of glycosylation at Y182 (P = 0.0015)
MVP		0.38
MPC		0.34
ClinPred		0.034	T
GERP RS		-1.9
Varity_R		0.11
gMVP		0.19
Mutation Taster		=89/11	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;