chr3-122119472-G-A

Position:

• chr3-122119472-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_175862.5(CD86):​c.928G>A​(p.Ala310Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 1,604,162 control chromosomes in the GnomAD database, including 71,297 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.26 (5761 hom., cov: 33)
  • Exomes 𝑓: 0.29 (65536 hom.)
• Consequence: CD86 NM_175862.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.778

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.8654267E-5).
• BP6: Variant 3-122119472-G-A is Benign according to our data. Variant chr3-122119472-G-A is described in ClinVar as [Benign]. Clinvar id is 1227026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD86	NM_175862.5	c.928G>A	p.Ala310Thr	missense_variant	7/7	ENST00000330540.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD86	ENST00000330540.7	c.928G>A	p.Ala310Thr	missense_variant	7/7	1	NM_175862.5	A2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39513 AN: 152020 Hom.: 5757 Cov.: 33

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.298

Gnomad NFE AF: 0.274

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.301 AC: 75387 AN: 250762 Hom.: 13121 AF XY: 0.312 AC XY: 42269 AN XY: 135550

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.602

Gnomad SAS exome AF: 0.448

Gnomad FIN exome AF: 0.326

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.292

GnomAD4 exome AF: 0.288 AC: 418110 AN: 1452022 Hom.: 65536 Cov.: 30 AF XY: 0.294 AC XY: 212357 AN XY: 722722

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.263

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.260 AC: 39519 AN: 152140 Hom.: 5761 Cov.: 33 AF XY: 0.267 AC XY: 19828 AN XY: 74370

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.596

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.274

Gnomad4 OTH AF: 0.258

Alfa AF: 0.274 Hom.: 15917

Bravo AF: 0.242

TwinsUK AF: 0.266 AC: 985

ALSPAC AF: 0.279 AC: 1076

ESP6500AA AF: 0.172 AC: 756

ESP6500EA AF: 0.260 AC: 2235

ExAC AF: 0.305 AC: 37008

Asia WGS AF: 0.509 AC: 1767 AN: 3478

EpiCase AF: 0.270

EpiControl AF: 0.269

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	This variant is associated with the following publications: (PMID: 25129060, 24298899, 16223675, 21870962, 21563968, 20380573, 20732370) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.7
DANN	Benign	0.93
DEOGEN2	Benign	0.35	.;.;T;.;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.64	T;T;T;T;T
MetaRNN	Benign	0.000039	T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	.;.;L;.;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.66	N;N;N;.;N
REVEL	Benign	0.031
Sift	Benign	0.18	T;T;T;.;T
Sift4G	Uncertain	0.037	D;D;D;D;D
Polyphen		0.0060	.;.;B;.;.
Vest4		0.077
MPC		0.31
ClinPred		0.018	T
GERP RS		3.2
Varity_R		0.044
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs1129055; hg19: chr3-121838319; COSMIC: COSV52605841;