rs4143815

Variant names:

• chr9-5468257-G-C
• rs4143815
• NM_014143.4:c.*395G>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.*395G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 284,046 control chromosomes in the GnomAD database, including 12,339 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 (5603 hom., cov: 32)
  • Exomes 𝑓: 0.30 (6736 hom.)
• Consequence: CD274 NM_014143.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 103 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

ENSG00000286162 (HGNC:56906):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.56 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.*395G>C		3_prime_UTR	Exon 7 of 7	NP_054862.1	Q9NZQ7-1
	CD274	NM_001267706.2		c.*395G>C		3_prime_UTR	Exon 6 of 6	NP_001254635.1	Q9NZQ7-2
	CD274	NR_052005.2		n.1164G>C		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD274	ENST00000381577.4	TSL:1 MANE Select	c.*395G>C		3_prime_UTR	Exon 7 of 7	ENSP00000370989.3	Q9NZQ7-1
	CD274	ENST00000381573.8	TSL:5	c.*395G>C		3_prime_UTR	Exon 6 of 6	ENSP00000370985.4	Q9NZQ7-2
	ENSG00000286162	ENST00000661858.1		n.277-9070C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36047 AN: 151910 Hom.: 5601 Cov.: 32

Gnomad AFR AF: 0.0559

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.251

GnomAD4 exome AF: 0.299 AC: 39482 AN: 132018 Hom.: 6736 Cov.: 0 AF XY: 0.300 AC XY: 19033 AN XY: 63498

African (AFR) AF: 0.0552 AC: 301 AN: 5456

American (AMR) AF: 0.378 AC: 1897 AN: 5022

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 1736 AN: 6474

East Asian (EAS) AF: 0.543 AC: 7298 AN: 13428

South Asian (SAS) AF: 0.188 AC: 837 AN: 4448

European-Finnish (FIN) AF: 0.286 AC: 993 AN: 3476

Middle Eastern (MID) AF: 0.262 AC: 200 AN: 762

European-Non Finnish (NFE) AF: 0.284 AC: 23559 AN: 83082

Other (OTH) AF: 0.270 AC: 2661 AN: 9870

GnomAD4 genome AF: 0.237 AC: 36045 AN: 152028 Hom.: 5603 Cov.: 32 AF XY: 0.241 AC XY: 17864 AN XY: 74276

African (AFR) AF: 0.0557 AC: 2311 AN: 41498

American (AMR) AF: 0.359 AC: 5480 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 927 AN: 3466

East Asian (EAS) AF: 0.578 AC: 2979 AN: 5156

South Asian (SAS) AF: 0.214 AC: 1031 AN: 4818

European-Finnish (FIN) AF: 0.277 AC: 2916 AN: 10528

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19456 AN: 67974

Other (OTH) AF: 0.249 AC: 527 AN: 2114

Alfa AF: 0.262 Hom.: 822

Bravo AF: 0.238

Asia WGS AF: 0.305 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.5
DANN	Benign	0.65
PhyloP100		0.12
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: rs4143815; hg19: chr9-5468257; COSMIC: COSV67501966;