NM_005191.4:c.256G>C

Variant names:

• chr3-119544712-C-G
• rs368745104
• NM_005191.4:c.256G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005191.4(CD80):​c.256G>C​(p.Glu86Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E86K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CD80 NM_005191.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 2 publications found

Genes affected

CD80 (HGNC:1700): (CD80 molecule) The protein encoded by this gene is a membrane receptor that is activated by the binding of CD28 or CTLA-4. The activated protein induces T-cell proliferation and cytokine production. This protein can act as a receptor for adenovirus subgroup B and may play a role in lupus neuropathy. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11867392).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005191.4. 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
	CD80	NM_005191.4	MANE Select	c.256G>C	p.Glu86Gln	missense	Exon 3 of 7	NP_005182.1	P33681-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD80	ENST00000264246.8	TSL:1 MANE Select	c.256G>C	p.Glu86Gln	missense	Exon 3 of 7	ENSP00000264246.3	P33681-1
	CD80	ENST00000478182.5	TSL:1	c.256G>C	p.Glu86Gln	missense	Exon 3 of 6	ENSP00000418364.1	P33681-1
	CD80	ENST00000383669.3	TSL:1	c.256G>C	p.Glu86Gln	missense	Exon 2 of 4	ENSP00000373165.3	P33681-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.48
DANN	Benign	0.78
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PhyloP100		-1.8
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.74	N
REVEL	Benign	0.010
Sift	Benign	0.072	T
Sift4G	Benign	0.19	T
Polyphen		0.044	B
Vest4		0.049
MutPred		0.39		Loss of ubiquitination at K88 (P = 0.0496)
MVP		0.30
MPC		0.17
ClinPred		0.48	T
GERP RS		-8.0
Varity_R		0.21
gMVP		0.67
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs368745104; hg19: chr3-119263559;