3-119537397-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005191.4(CD80):ā€‹c.440T>Cā€‹(p.Ile147Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

CD80
NM_005191.4 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40079042).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD80NM_005191.4 linkuse as main transcriptc.440T>C p.Ile147Thr missense_variant 4/7 ENST00000264246.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD80ENST00000264246.8 linkuse as main transcriptc.440T>C p.Ile147Thr missense_variant 4/71 NM_005191.4 P2P33681-1
CD80ENST00000478182.5 linkuse as main transcriptc.440T>C p.Ile147Thr missense_variant 4/61 P2P33681-1
CD80ENST00000383669.3 linkuse as main transcriptc.440T>C p.Ile147Thr missense_variant 3/41 A2P33681-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.87e-7
AC:
1
AN:
1456652
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725134
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 08, 2022The c.440T>C (p.I147T) alteration is located in exon 4 (coding exon 3) of the CD80 gene. This alteration results from a T to C substitution at nucleotide position 440, causing the isoleucine (I) at amino acid position 147 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Benign
-0.00053
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.91
D;D;.
Eigen
Uncertain
0.27
Eigen_PC
Benign
0.10
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.56
.;T;T
M_CAP
Benign
0.067
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Benign
-0.40
T
MutationAssessor
Uncertain
2.3
M;M;M
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-4.0
D;D;D
REVEL
Uncertain
0.36
Sift
Pathogenic
0.0
D;D;D
Sift4G
Uncertain
0.044
D;D;T
Polyphen
0.99
D;D;.
Vest4
0.28
MutPred
0.58
Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);Gain of disorder (P = 0.0172);
MVP
0.89
MPC
0.75
ClinPred
0.98
D
GERP RS
4.0
Varity_R
0.50
gMVP
0.49

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs768035102; hg19: chr3-119256244; API