Variant rs4143815 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014143.4(CD274):c.*395G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 284,046 control chromosomes in the GnomAD database, including 12,339 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5603 hom., cov: 32)

Exomes 𝑓: 0.30 ( 6736 hom. )

Consequence

CD274
NM_014143.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.122

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]

CD274 links:

ENSG00000286162 (HGNC:):

ENSG00000286162 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD274	NM_014143.4 link	c.*395G>C		3_prime_UTR_variant	7/7	ENST00000381577.4	NP_054862.1	Q9NZQ7-1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CD274	ENST00000381577.4 link	c.*395G>C	3_prime_UTR_variant	7/7	1	NM_014143.4	ENSP00000370989.3	Q9NZQ7-1
CD274	ENST00000381573.8 link	c.*395G>C	3_prime_UTR_variant	6/6	5		ENSP00000370985.4	Q9NZQ7-2
ENSG00000286162	ENST00000661858.1 link	n.277-9070C>G	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36047

AN:

151910

Hom.:

5601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0559

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.359

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.576

Gnomad SAS

AF:

0.214

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.251

GnomAD4 exome

AF:

0.299

AC:

39482

AN:

132018

Hom.:

6736

Cov.:

AF XY:

0.300

AC XY:

19033

AN XY:

63498

show subpopulations

Gnomad4 AFR exome

AF:

0.0552

Gnomad4 AMR exome

AF:

0.378

Gnomad4 ASJ exome

AF:

0.268

Gnomad4 EAS exome

AF:

0.543

Gnomad4 SAS exome

AF:

0.188

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.237

AC:

36045

AN:

152028

Hom.:

5603

Cov.:

AF XY:

0.241

AC XY:

17864

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0557

Gnomad4 AMR

AF:

0.359

Gnomad4 ASJ

AF:

0.267

Gnomad4 EAS

AF:

0.578

Gnomad4 SAS

AF:

0.214

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.262

Hom.:

822

Bravo

AF:

0.238

Asia WGS

AF:

0.305

AC:

1056

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

1.5

DANN

Benign

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over