rs770820543

Variant names:

• chr3-119544585-C-G
• rs770820543
• NM_005191.4:c.383G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-119544585-C-G
• chr3-119544585-C-T

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.383G>C​(p.Arg128Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,810 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R128Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD80 NM_005191.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.913
• Publications: 0 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=0.18807119).

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.383G>C	p.Arg128Pro	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.383G>C	p.Arg128Pro	missense	Exon 3 of 7	ENSP00000264246.3	P33681-1
	CD80	ENST00000478182.5	TSL:1	c.383G>C	p.Arg128Pro	missense	Exon 3 of 6	ENSP00000418364.1	P33681-1
	CD80	ENST00000383669.3	TSL:1	c.383G>C	p.Arg128Pro	missense	Exon 2 of 4	ENSP00000373165.3	P33681-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727194

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111952

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	9.9
DANN	Benign	0.92
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.91
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.23
Sift	Benign	0.13	T
Sift4G	Uncertain	0.058	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.54		Loss of ubiquitination at K127 (P = 0.0531)
MVP		0.77
MPC		0.76
ClinPred		0.54	D
GERP RS		-8.0
Varity_R		0.48
gMVP		0.84
Mutation Taster		=90/10	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: rs770820543; hg19: chr3-119263432;