rs822342

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD274	NM_014143.4	c.-14-2127T>C		intron_variant	Intron 1 of 6	ENST00000381577.4	NP_054862.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD274	ENST00000381577.4	c.-14-2127T>C		intron_variant	Intron 1 of 6	1	NM_014143.4	ENSP00000370989.3
CD274	ENST00000381573.8	c.-14-2127T>C		intron_variant	Intron 1 of 5	5		ENSP00000370985.4

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

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.683

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.751

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.791

Alfa AF: 0.754 Hom.: 5434

Bravo AF: 0.766

Asia WGS AF: 0.665 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.79

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: rs822342; hg19: chr9-5453973;