chr9-5453973-T-C

Variant names:

• chr9-5453973-T-C
• rs822342
• NM_014143.4:c.-14-2127T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014143.4(CD274):​c.-14-2127T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,174 control chromosomes in the GnomAD database, including 45,804 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 0.77 (45804 hom., cov: 32)
• Consequence: CD274 NM_014143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 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.-14-2127T>C		intron	N/A	NP_054862.1	Q9NZQ7-1
	CD274	NM_001314029.2		c.-14-2127T>C		intron	N/A	NP_001300958.1	Q9NZQ7-4
	CD274	NM_001267706.2		c.-14-2127T>C		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.-14-2127T>C		intron	N/A	ENSP00000370989.3	Q9NZQ7-1
	CD274	ENST00000381573.8	TSL:5	c.-14-2127T>C		intron	N/A	ENSP00000370985.4	Q9NZQ7-2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116966 AN: 152056 Hom.: 45751 Cov.: 32

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.751

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.789

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

GnomAD4 genome AF: 0.769 AC: 117068 AN: 152174 Hom.: 45804 Cov.: 32 AF XY: 0.763 AC XY: 56765 AN XY: 74406

African (AFR) AF: 0.895 AC: 37189 AN: 41540

American (AMR) AF: 0.683 AC: 10437 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2745 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2333 AN: 5166

South Asian (SAS) AF: 0.751 AC: 3623 AN: 4826

European-Finnish (FIN) AF: 0.739 AC: 7816 AN: 10578

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.742 AC: 50424 AN: 67990

Other (OTH) AF: 0.791 AC: 1670 AN: 2112

Alfa AF: 0.760 Hom.: 5754

Bravo AF: 0.766

Asia WGS AF: 0.665 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.79
PhyloP100		0.058
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: rs822342; hg19: chr9-5453973;