9-5455732-T-G

Position:

• chr9-5455732-T-G

Variant summary

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

The NM_014143.4(CD274):​c.-14-368T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,064 control chromosomes in the GnomAD database, including 5,320 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 (5320 hom., cov: 32)
• Consequence: CD274 NM_014143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.414

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD274	NM_014143.4	c.-14-368T>G		intron_variant		ENST00000381577.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD274	ENST00000381577.4	c.-14-368T>G		intron_variant		1	NM_014143.4	P1
CD274	ENST00000381573.8	c.-14-368T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36543 AN: 151946 Hom.: 5308 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.603

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.219

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.240 AC: 36558 AN: 152064 Hom.: 5320 Cov.: 32 AF XY: 0.249 AC XY: 18501 AN XY: 74328

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.217

Alfa AF: 0.233 Hom.: 2082

Bravo AF: 0.244

Asia WGS AF: 0.362 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.86

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: rs2282055; hg19: chr9-5455732; COSMIC: COSV67501763; COSMIC: COSV67501763;