rs2297136

chr9-5467955-G-Achr9-5467955-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014143.4(CD274):c.*93G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,092,952 control chromosomes in the GnomAD database, including 165,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.56 (24547 hom., cov: 30)
  • Exomes 𝑓: 0.54 (141140 hom.)
• Consequence: CD274 NM_014143.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.710

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 9-5467955-G-A is Benign according to our data. Variant chr9-5467955-G-A is described in ClinVar as [Benign]. Clinvar id is 1251725.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD274	NM_014143.4	c.*93G>A		3_prime_UTR_variant	7/7	ENST00000381577.4
LOC124902114	XR_007061406.1	n.256-8768C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD274	ENST00000381577.4	c.*93G>A		3_prime_UTR_variant	7/7	1	NM_014143.4	P1
	ENST00000661858.1	n.277-8768C>T		intron_variant, non_coding_transcript_variant
CD274	ENST00000381573.8	c.*93G>A		3_prime_UTR_variant	6/6	5

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85540 AN: 151754 Hom.: 24528 Cov.: 30

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.579

GnomAD4 exome AF: 0.540 AC: 508465 AN: 941080 Hom.: 141140 Cov.: 12 AF XY: 0.542 AC XY: 265139 AN XY: 489406

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.712

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.799

Gnomad4 SAS exome AF: 0.593

Gnomad4 FIN exome AF: 0.427

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.564 AC: 85604 AN: 151872 Hom.: 24547 Cov.: 30 AF XY: 0.565 AC XY: 41912 AN XY: 74208

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.580

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.583

Alfa AF: 0.537 Hom.: 22173

Bravo AF: 0.585

Asia WGS AF: 0.700 AC: 2436 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 17, 2020

This variant is associated with the following publications: (PMID: 28677815) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	5.4
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2297136; hg19: chr9-5467955; COSMIC: COSV67501259; COSMIC: COSV67501259;