rs1411262

Positions:

• chr9-5459419-C-T

Variant summary

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

The ENST00000381577.4(CD274):​c.394+1999C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 151,920 control chromosomes in the GnomAD database, including 8,793 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 0.33 (8793 hom., cov: 32)
• Consequence: CD274 ENST00000381577.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD274	NM_014143.4	c.394+1999C>T		intron_variant		ENST00000381577.4	NP_054862.1
LOC124902114	XR_007061406.1	n.256-232G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD274	ENST00000381577.4	c.394+1999C>T		intron_variant		1	NM_014143.4	ENSP00000370989	P1
	ENST00000661858.1	n.277-232G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49613 AN: 151802 Hom.: 8775 Cov.: 32

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.287

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

GnomAD4 genome AF: 0.327 AC: 49678 AN: 151920 Hom.: 8793 Cov.: 32 AF XY: 0.330 AC XY: 24489 AN XY: 74238

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.357

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.285

Alfa AF: 0.274 Hom.: 12253

Bravo AF: 0.343

Asia WGS AF: 0.363 AC: 1261 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.47

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: rs1411262; hg19: chr9-5459419;