rs2681417

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr3-122106350-G-A
• chr3-122106350-G-C
• chr3-122106350-G-T

Variant summary

Our verdict is Benign. The variant received -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. 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. V185F) has been classified as Uncertain significance.

• 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
• 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: Benign. The variant received -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.

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>A	p.Val185Ile	missense	Exon 4 of 7	NP_787058.5
	CD86	NM_006889.5		c.535G>A	p.Val179Ile	missense	Exon 4 of 7	NP_008820.4	P42081-3
	CD86	NM_176892.2		c.535G>A	p.Val179Ile	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>A	p.Val185Ile	missense	Exon 4 of 7	ENSP00000332049.2	P42081-1
	CD86	ENST00000393627.6	TSL:1	c.535G>A	p.Val179Ile	missense	Exon 4 of 7	ENSP00000377248.2	P42081-3
	CD86	ENST00000478741.1	TSL:5	c.538G>A	p.Val180Ile	missense	Exon 3 of 5	ENSP00000417195.1	H7C4F8

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

GnomAD2 exomes AF: 0.920 AC: 231168 AN: 251134 AF XY: 0.921

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 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

African (AFR) AF: 0.665 AC: 22240 AN: 33468

American (AMR) AF: 0.949 AC: 42458 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.948 AC: 24758 AN: 26128

East Asian (EAS) AF: 0.997 AC: 39575 AN: 39694

South Asian (SAS) AF: 0.892 AC: 76960 AN: 86248

European-Finnish (FIN) AF: 0.958 AC: 51155 AN: 53416

Middle Eastern (MID) AF: 0.917 AC: 5292 AN: 5768

European-Non Finnish (NFE) AF: 0.930 AC: 1033944 AN: 1111854

Other (OTH) AF: 0.916 AC: 55325 AN: 60382

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

African (AFR) AF: 0.678 AC: 28107 AN: 41450

American (AMR) AF: 0.922 AC: 14093 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3285 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5167 AN: 5182

South Asian (SAS) AF: 0.894 AC: 4312 AN: 4822

European-Finnish (FIN) AF: 0.956 AC: 10142 AN: 10608

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.928 AC: 63157 AN: 68022

Other (OTH) AF: 0.873 AC: 1845 AN: 2114

Alfa AF: 0.908 Hom.: 218876

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 v4.9

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
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	7.8e-7	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.1
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.048
Sift	Benign	0.34	T
Sift4G	Benign	0.15	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
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

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