3-122119944-T-C

Position:

• chr3-122119944-T-C

Variant summary

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

The NM_175862.5(CD86):​c.*410T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.60 (7830 hom., cov: 24)
  • Exomes 𝑓: 0.29 (1096 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD86 NM_175862.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.270

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=-0.91).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD86	NM_175862.5	c.*410T>C		3_prime_UTR_variant	7/7	ENST00000330540.7	NP_787058.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7	c.*410T>C		3_prime_UTR_variant	7/7	1	NM_175862.5	ENSP00000332049.2
CD86	ENST00000264468.9	c.*410T>C		3_prime_UTR_variant	6/6	5		ENSP00000264468.6
CD86	ENST00000469710.5	c.*410T>C		3_prime_UTR_variant	6/6	2		ENSP00000418988.1
CD86	ENST00000493101.5	c.*410T>C		3_prime_UTR_variant	6/6	2		ENSP00000420230.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 46305 AN: 77326 Hom.: 7824 Cov.: 24 FAILED QC

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.609

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.294 AC: 5878 AN: 19980 Hom.: 1096 Cov.: 0 AF XY: 0.312 AC XY: 3125 AN XY: 10032

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.599 AC: 46319 AN: 77342 Hom.: 7830 Cov.: 24 AF XY: 0.602 AC XY: 23208 AN XY: 38530

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.568

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.609

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.599

Alfa AF: 0.323 Hom.: 6407

Bravo AF: 0.282

Asia WGS AF: 0.641 AC: 1989 AN: 3110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.52

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: rs1915087; hg19: chr3-121838791; COSMIC: COSV105093533; COSMIC: COSV105093533;