rs1970000

Positions:

• chr9-5465036-C-A
• chr9-5465036-C-G
• chr9-5465036-C-T

Variant summary

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

The NM_014143.4(CD274):​c.683-463C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 149,956 control chromosomes in the GnomAD database, including 25,056 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 0.57 (25056 hom., cov: 25)
• Consequence: CD274 NM_014143.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD274	NM_014143.4	c.683-463C>A		intron_variant		ENST00000381577.4	NP_054862.1
LOC124902114	XR_007061406.1	n.256-5849G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD274	ENST00000381577.4	c.683-463C>A		intron_variant		1	NM_014143.4	ENSP00000370989	P1
	ENST00000661858.1	n.277-5849G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.568 AC: 85160 AN: 149846 Hom.: 25008 Cov.: 25

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.635

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.569 AC: 85257 AN: 149956 Hom.: 25056 Cov.: 25 AF XY: 0.571 AC XY: 41693 AN XY: 72970

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.635

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.889

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.566

Alfa AF: 0.509 Hom.: 2469

Bravo AF: 0.591

Asia WGS AF: 0.722 AC: 2510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.97
DANN	Benign	0.42

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: rs1970000; hg19: chr9-5465036; COSMIC: COSV67501835; COSMIC: COSV67501835;