ENST00000393627.6:c.-129G>A

Variant names:

• chr3-122077921-G-A
• rs9282641
• ENST00000393627.6:c.-129G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000393627.6(CD86):​c.-129G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0824 in 985,330 control chromosomes in the GnomAD database, including 3,529 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 0.070 (439 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3090 hom.)
• Consequence: CD86 ENST00000393627.6 5_prime_UTR
• Scores: Splicing: ADA: 0.00002264
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.755
• Publications: 69 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]

ENSG00000306536 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393627.6. 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.15-13680G>A		intron	N/A	NP_787058.5
	CD86	NM_006889.5		c.-129G>A		5_prime_UTR	Exon 1 of 7	NP_008820.4	P42081-3
	CD86	NM_176892.2		c.-129G>A		5_prime_UTR	Exon 1 of 6	NP_795711.2	P42081-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD86	ENST00000393627.6	TSL:1	c.-129G>A		5_prime_UTR	Exon 1 of 7	ENSP00000377248.2	P42081-3
	CD86	ENST00000330540.7	TSL:1 MANE Select	c.15-13680G>A		intron	N/A	ENSP00000332049.2	P42081-1
	CD86	ENST00000264468.9	TSL:5	c.-129G>A		5_prime_UTR	Exon 1 of 6	ENSP00000264468.6	P42081-4

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10676 AN: 152112 Hom.: 438 Cov.: 32

Gnomad AFR AF: 0.0387

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0686

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0769

GnomAD4 exome AF: 0.0846 AC: 70507 AN: 833100 Hom.: 3090 Cov.: 30 AF XY: 0.0849 AC XY: 32666 AN XY: 384734

African (AFR) AF: 0.0337 AC: 532 AN: 15786

American (AMR) AF: 0.0650 AC: 64 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 632 AN: 5156

East Asian (EAS) AF: 0.000551 AC: 2 AN: 3632

South Asian (SAS) AF: 0.109 AC: 1790 AN: 16460

European-Finnish (FIN) AF: 0.102 AC: 31 AN: 304

Middle Eastern (MID) AF: 0.102 AC: 166 AN: 1620

European-Non Finnish (NFE) AF: 0.0855 AC: 65104 AN: 761856

Other (OTH) AF: 0.0801 AC: 2186 AN: 27302

GnomAD4 genome AF: 0.0701 AC: 10673 AN: 152230 Hom.: 439 Cov.: 32 AF XY: 0.0710 AC XY: 5286 AN XY: 74416

African (AFR) AF: 0.0385 AC: 1601 AN: 41536

American (AMR) AF: 0.0686 AC: 1048 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0958 AC: 461 AN: 4814

European-Finnish (FIN) AF: 0.0868 AC: 919 AN: 10588

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.0873 AC: 5942 AN: 68026

Other (OTH) AF: 0.0756 AC: 160 AN: 2116

Alfa AF: 0.0838 Hom.: 2574

Bravo AF: 0.0665

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.63
PhyloP100		0.76
PromoterAI		-0.056	Neutral
Mutation Taster		=299/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs9282641;

hg19: chr3-121796768;