rs2681417

chr3-122106350-G-Achr3-122106350-G-Cchr3-122106350-G-T

Variant summary

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

The NM_175862.5(CD86):c.553G>A(p.Val185Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 1,613,848 control chromosomes in the GnomAD database, including 684,103 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.86 (57566 hom., cov: 31)
  • Exomes 𝑓: 0.92 (626537 hom.)
• 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.7700014E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD86	NM_175862.5	c.553G>A	p.Val185Ile	missense_variant	4/7	ENST00000330540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.553G>A	p.Val185Ile	missense_variant	4/7	1	NM_175862.5	A2

Frequencies

GnomAD3 genomes AF: 0.862 AC: 131085 AN: 152048 Hom.: 57541 Cov.: 31

Gnomad AFR AF: 0.678

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.918

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.872

GnomAD3 exomes AF: 0.920 AC: 231168 AN: 251134 Hom.: 107036 AF XY: 0.921 AC XY: 124992 AN XY: 135712

Gnomad AFR exome AF: 0.677

Gnomad AMR exome AF: 0.954

Gnomad ASJ exome AF: 0.946

Gnomad EAS exome AF: 0.997

Gnomad SAS exome AF: 0.894

Gnomad FIN exome AF: 0.959

Gnomad NFE exome AF: 0.930

Gnomad OTH exome AF: 0.934

GnomAD4 exome AF: 0.925 AC: 1351707 AN: 1461682 Hom.: 626537 Cov.: 52 AF XY: 0.924 AC XY: 672155 AN XY: 727144

Gnomad4 AFR exome AF: 0.665

Gnomad4 AMR exome AF: 0.949

Gnomad4 ASJ exome AF: 0.948

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.892

Gnomad4 FIN exome AF: 0.958

Gnomad4 NFE exome AF: 0.930

Gnomad4 OTH exome AF: 0.916

GnomAD4 genome AF: 0.862 AC: 131156 AN: 152166 Hom.: 57566 Cov.: 31 AF XY: 0.866 AC XY: 64414 AN XY: 74408

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 0.946

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.894

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.873

Alfa AF: 0.918 Hom.: 161086

Bravo AF: 0.853

TwinsUK AF: 0.932 AC: 3457

ALSPAC AF: 0.934 AC: 3598

ESP6500AA AF: 0.688 AC: 3031

ESP6500EA AF: 0.930 AC: 8002

ExAC AF: 0.914 AC: 110946

Asia WGS AF: 0.916 AC: 3182 AN: 3476

EpiCase AF: 0.928

EpiControl AF: 0.926

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
Cadd	Benign	1.7
Dann	Benign	0.92
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.53	T;T;T;T;T
MetaRNN	Benign	7.8e-7	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.20	N;N;N;.;N
REVEL	Benign	0.048
Sift	Benign	0.34	T;T;T;.;T
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.0090	.;.;B;.;.
Vest4		0.019
MPC		0.27
ClinPred		0.0069	T
GERP RS		-1.9
Varity_R		0.063
gMVP		0.099

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: rs2681417; hg19: chr3-121825197; COSMIC: COSV52608918; COSMIC: COSV52608918;