Variant rs2681417 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.10

Variant links:

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]

CD86 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	c.553G>A	p.Val185Ile	missense_variant	4/7	1	NM_175862.5	A2	P42081-1

Frequencies

GnomAD3 genomes

AF:

0.862

AC:

131085

AN:

152048

Hom.:

57541

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.924

AC XY:

672155

AN XY:

727144

show subpopulations

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.:

AF XY:

0.866

AC XY:

64414

AN XY:

74408

show subpopulations

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

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

LIST_S2

Benign

0.53

T;T;T;T;T

MetaRNN

Benign

7.8e-7

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;.;L;.;.

MutationTaster

Benign

1.0

P;P;P;P;P

PrimateAI

Benign

0.29

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over