Variant rs2297136 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.710

Variant links:

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
CD274	NM_014143.4 linkuse as main transcript	c.*93G>A		3_prime_UTR_variant	7/7	ENST00000381577.4	NP_054862.1
LOC124902114	XR_007061406.1 linkuse as main transcript	n.256-8768C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD274	ENST00000381577.4 linkuse as main transcript	c.*93G>A	3_prime_UTR_variant	7/7	1	NM_014143.4	ENSP00000370989	P1	Q9NZQ7-1
	ENST00000661858.1 linkuse as main transcript	n.277-8768C>T	intron_variant, non_coding_transcript_variant
CD274	ENST00000381573.8 linkuse as main transcript	c.*93G>A	3_prime_UTR_variant	6/6	5		ENSP00000370985		Q9NZQ7-2

Frequencies

GnomAD3 genomes

AF:

0.564

AC:

85540

AN:

151754

Hom.:

24528

Cov.:

show subpopulations

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.:

AF XY:

0.542

AC XY:

265139

AN XY:

489406

show subpopulations

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.:

AF XY:

0.565

AC XY:

41912

AN XY:

74208

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 17, 2020	This variant is associated with the following publications: (PMID: 28677815) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over