chr9-5455732-T-G

Variant names:

• chr9-5455732-T-G
• rs2282055
• NM_014143.4:c.-14-368T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 45 publications found

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 Gene-Disease associations (from GenCC):

• neonatal diabetes mellitus

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014143.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD274	NM_014143.4	MANE Select	c.-14-368T>G		intron	N/A	NP_054862.1	Q9NZQ7-1
	CD274	NM_001314029.2		c.-14-368T>G		intron	N/A	NP_001300958.1	Q9NZQ7-4
	CD274	NM_001267706.2		c.-14-368T>G		intron	N/A	NP_001254635.1	Q9NZQ7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD274	ENST00000381577.4	TSL:1 MANE Select	c.-14-368T>G		intron	N/A	ENSP00000370989.3	Q9NZQ7-1
	CD274	ENST00000381573.8	TSL:5	c.-14-368T>G		intron	N/A	ENSP00000370985.4	Q9NZQ7-2

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

African (AFR) AF: 0.107 AC: 4427 AN: 41510

American (AMR) AF: 0.350 AC: 5343 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 729 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3125 AN: 5172

South Asian (SAS) AF: 0.271 AC: 1309 AN: 4822

European-Finnish (FIN) AF: 0.279 AC: 2953 AN: 10574

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17837 AN: 67944

Other (OTH) AF: 0.217 AC: 458 AN: 2110

Alfa AF: 0.242 Hom.: 3036

Bravo AF: 0.244

Asia WGS AF: 0.362 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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