3-122119511-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_175862.5(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 NM_175862.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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 -14 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_single_submitter, 1 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 GnomAd at 1371 AD gene.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.967G>A	p.Asp323Asn	missense_variant	7/7	1	NM_175862.5	A2

Frequencies

GnomAD3 genomes AF: 0.00901 AC: 1371 AN: 152184 Hom.: 18 Cov.: 33

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.: 10 AF XY: 0.00169 AC XY: 230 AN XY: 135704

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.: 22 Cov.: 27 AF XY: 0.00107 AC XY: 770 AN XY: 721694

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.: 18 Cov.: 33 AF XY: 0.00876 AC XY: 652 AN XY: 74466

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.: 9

Bravo AF: 0.0112

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0254 AC: 112

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.00289 AC: 351

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	4.0
Dann	Benign	0.91
Eigen	Benign	-0.83
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.75	T;T;T;T;T
MetaRNN	Benign	0.0038	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.29	T
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	T
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

Other links and lift over

dbSNP: rs9282648; hg19: chr3-121838358; COSMIC: COSV99043186;