3-122106350-G-C

Position:

• chr3-122106350-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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. V185I) has been classified as Likely benign.

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

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08086097).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD86	NM_175862.5	c.553G>C	p.Val185Leu	missense_variant	4/7	ENST00000330540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.553G>C	p.Val185Leu	missense_variant	4/7	1	NM_175862.5	A2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 52

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;T;T;T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.081	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	.;.;L;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N;N;N;.;N
REVEL	Benign	0.048
Sift	Benign	0.44	T;T;T;.;T
Sift4G	Benign	0.22	T;T;T;T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2681417; hg19: chr3-121825197;