Variant 3-122119511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000330540.7(CD86):c.967G>A(p.Asp323Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,601,248 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0090 ( 18 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 22 hom. )

Consequence

CD86
ENST00000330540.7 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.06

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037780702).

BP6

Variant 3-122119511-G-A is Benign according to our data. Variant chr3-122119511-G-A is described in ClinVar as [Benign]. Clinvar id is 720917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.009 (1370/152302) while in subpopulation AFR AF= 0.0296 (1230/41550). AF 95% confidence interval is 0.0282. There are 18 homozygotes in gnomad4. There are 652 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1370 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD86	NM_175862.5 linkuse as main transcript	c.967G>A	p.Asp323Asn	missense_variant	7/7	ENST00000330540.7	NP_787058.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7 linkuse as main transcript	c.967G>A	p.Asp323Asn	missense_variant	7/7	1	NM_175862.5	ENSP00000332049	A2	P42081-1

Frequencies

GnomAD3 genomes

AF:

0.00901

AC:

1371

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00245

AC:

615

AN:

251002

Hom.:

AF XY:

0.00169

AC XY:

230

AN XY:

135704

show subpopulations

Gnomad AFR exome

AF:

0.0304

Gnomad AMR exome

AF:

0.00215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00116

AC:

1681

AN:

1448946

Hom.:

Cov.:

AF XY:

0.00107

AC XY:

770

AN XY:

721694

show subpopulations

Gnomad4 AFR exome

AF:

0.0295

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000363

Gnomad4 OTH exome

AF:

0.00254

GnomAD4 genome

AF:

0.00900

AC:

1370

AN:

152302

Hom.:

Cov.:

AF XY:

0.00876

AC XY:

652

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0296

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00251

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0254

AC:

112

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00289

AC:

351

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.77

CADD

Benign

4.0

DANN

Benign

0.91

DEOGEN2

Benign

0.34

.;.;T;.;.

Eigen

Benign

-0.83

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0091

LIST_S2

Benign

0.75

T;T;T;T;T

MetaRNN

Benign

0.0038

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

.;.;N;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.93

N;N;N;.;N

REVEL

Benign

0.042

Sift

Benign

0.19

T;T;T;.;T

Sift4G

Benign

0.25

T;T;T;T;T

Polyphen

0.44

.;.;B;.;.

Vest4

0.029

MVP

0.53

MPC

0.30

ClinPred

0.0049

GERP RS

-2.7

Varity_R

0.024

gMVP

0.053

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over