GeneBe

rs17718883

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014143.4(CD274):​c.437C>A​(p.Pro146Gln) 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 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CD274
NM_014143.4 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.835
Variant links:
Genes affected
CD274 (HGNC:17635): (CD274 molecule) This gene encodes an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells. The encoded protein is a type I transmembrane protein that has immunoglobulin V-like and C-like domains. Interaction of this ligand with its receptor inhibits T-cell activation and cytokine production. During infection or inflammation of normal tissue, this interaction is important for preventing autoimmunity by maintaining homeostasis of the immune response. In tumor microenvironments, this interaction provides an immune escape for tumor cells through cytotoxic T-cell inactivation. Expression of this gene in tumor cells is considered to be prognostic in many types of human malignancies, including colon cancer and renal cell carcinoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22633323).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD274NM_014143.4 linkc.437C>A p.Pro146Gln missense_variant Exon 4 of 7 ENST00000381577.4 NP_054862.1 Q9NZQ7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD274ENST00000381577.4 linkc.437C>A p.Pro146Gln missense_variant Exon 4 of 7 1 NM_014143.4 ENSP00000370989.3 Q9NZQ7-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461590
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727092
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
21
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.57
.;D
Eigen
Benign
0.18
Eigen_PC
Benign
0.065
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.053
D
MetaRNN
Benign
0.23
T;T
MetaSVM
Benign
-0.44
T
MutationAssessor
Uncertain
2.4
.;M
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Benign
0.070
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
0.99
.;D
Vest4
0.14
MutPred
0.35
.;Loss of phosphorylation at T148 (P = 0.1031);
MVP
0.49
MPC
0.59
ClinPred
0.94
D
GERP RS
4.0
Varity_R
0.41
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-5462876; API