chr3-122074643-G-A

Position:

• chr3-122074643-G-A

Variant summary

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

The NM_175862.5(CD86):​c.15-16958G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,160 control chromosomes in the GnomAD database, including 1,048 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 0.11 (1048 hom., cov: 32)
• Consequence: CD86 NM_175862.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD86	NM_175862.5	c.15-16958G>A		intron_variant		ENST00000330540.7	NP_787058.5
CD86	NM_001206924.2	c.15-16958G>A		intron_variant			NP_001193853.2
CD86	NM_001206925.2	c.-183+19140G>A		intron_variant			NP_001193854.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD86	ENST00000330540.7	c.15-16958G>A		intron_variant		1	NM_175862.5	ENSP00000332049	A2
CD86	ENST00000469710.5	c.-183+19140G>A		intron_variant		2		ENSP00000418988
CD86	ENST00000493101.5	c.15-16958G>A		intron_variant		2		ENSP00000420230
CD86	ENST00000478390.1	n.128-16958G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17323 AN: 152042 Hom.: 1048 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0835

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.0485

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.114 AC: 17327 AN: 152160 Hom.: 1048 Cov.: 32 AF XY: 0.112 AC XY: 8302 AN XY: 74380

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.0744

Gnomad4 EAS AF: 0.00755

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.102

Alfa AF: 0.119 Hom.: 181

Bravo AF: 0.111

Asia WGS AF: 0.0360 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.38

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: rs2715260; hg19: chr3-121793490;