3-122120794-G-C

Position:

• chr3-122120794-G-C

Variant summary

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

The NM_175862.5(CD86):​c.*1260G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,660 control chromosomes in the GnomAD database, including 1,420 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.14 (1416 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4 hom.)
• Consequence: CD86 NM_175862.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD86	NM_175862.5	c.*1260G>C		3_prime_UTR_variant	7/7	ENST00000330540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.*1260G>C		3_prime_UTR_variant	7/7	1	NM_175862.5	A2
CD86	ENST00000264468.9	c.*1260G>C		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20599 AN: 152088 Hom.: 1415 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.123 AC: 56 AN: 454 Hom.: 4 Cov.: 0 AF XY: 0.121 AC XY: 30 AN XY: 248

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.0152

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.0556

GnomAD4 genome AF: 0.135 AC: 20609 AN: 152206 Hom.: 1416 Cov.: 32 AF XY: 0.135 AC XY: 10048 AN XY: 74416

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.0508

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0670 Hom.: 78

Bravo AF: 0.131

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.48
DANN	Benign	0.47

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: rs17281995; hg19: chr3-121839641;