chr3-122063104-T-A

Position:

• chr3-122063104-T-A

Variant summary

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

The NM_175862.5(CD86):​c.14+7601T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,202 control chromosomes in the GnomAD database, including 2,652 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 0.18 (2652 hom., cov: 32)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD86	NM_175862.5	c.14+7601T>A		intron_variant		ENST00000330540.7	NP_787058.5
CD86	NM_001206925.2	c.-183+7601T>A		intron_variant			NP_001193854.2
CD86	NM_001206924.2	c.14+7601T>A		intron_variant			NP_001193853.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7	c.14+7601T>A		intron_variant		1	NM_175862.5	ENSP00000332049.2
CD86	ENST00000469710.5	c.-183+7601T>A		intron_variant		2		ENSP00000418988.1
CD86	ENST00000493101.5	c.14+7601T>A		intron_variant		2		ENSP00000420230.1
CD86	ENST00000478390.1	n.127+7601T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27668 AN: 152084 Hom.: 2648 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00923

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.171

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.182 AC: 27694 AN: 152202 Hom.: 2652 Cov.: 32 AF XY: 0.179 AC XY: 13297 AN XY: 74416

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00926

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.170

Alfa AF: 0.190 Hom.: 348

Bravo AF: 0.179

Asia WGS AF: 0.110 AC: 381 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.29

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: rs2715273; hg19: chr3-121781951;