rs4143815

chr9-5468257-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122

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]

(HGNC:):

ACMG classification

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	UniProt
CD274	NM_014143.4	c.*395G>C		3_prime_UTR_variant	7/7	ENST00000381577.4
LOC124902114	XR_007061406.1	n.256-9070C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD274	ENST00000381577.4	c.*395G>C		3_prime_UTR_variant	7/7	1	NM_014143.4	P1
	ENST00000661858.1	n.277-9070C>G		intron_variant, non_coding_transcript_variant
CD274	ENST00000381573.8	c.*395G>C		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36047 AN: 151910 Hom.: 5601 Cov.: 32

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.: 0 AF XY: 0.300 AC XY: 19033 AN XY: 63498

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.: 32 AF XY: 0.241 AC XY: 17864 AN XY: 74276

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

Other links and lift over

dbSNP: rs4143815; hg19: chr9-5468257; COSMIC: COSV67501966; COSMIC: COSV67501966;