Variant chr9-5465732-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014143.4(CD274):c.790+126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 604,260 control chromosomes in the GnomAD database, including 17,279 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 0.18 ( 3458 hom., cov: 32)

Exomes 𝑓: 0.23 ( 13821 hom. )

Consequence

CD274
NM_014143.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.239

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.467 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.790+126G>A		intron_variant		ENST00000381577.4	NP_054862.1
LOC124902114	XR_007061406.1 linkuse as main transcript	n.256-6545C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD274	ENST00000381577.4 linkuse as main transcript	c.790+126G>A		intron_variant		1	NM_014143.4	ENSP00000370989	P1	Q9NZQ7-1
	ENST00000661858.1 linkuse as main transcript	n.277-6545C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28122

AN:

152096

Hom.:

3455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0434

Gnomad AMI

AF:

0.325

Gnomad AMR

AF:

0.270

Gnomad ASJ

AF:

0.179

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.234

AC:

105664

AN:

452046

Hom.:

13821

Cov.:

AF XY:

0.232

AC XY:

55747

AN XY:

240124

show subpopulations

Gnomad4 AFR exome

AF:

0.0436

Gnomad4 AMR exome

AF:

0.298

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.475

Gnomad4 SAS exome

AF:

0.177

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.225

Gnomad4 OTH exome

AF:

0.213

GnomAD4 genome

AF:

0.185

AC:

28121

AN:

152214

Hom.:

3458

Cov.:

AF XY:

0.190

AC XY:

14137

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0432

Gnomad4 AMR

AF:

0.270

Gnomad4 ASJ

AF:

0.179

Gnomad4 EAS

AF:

0.483

Gnomad4 SAS

AF:

0.180

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.222

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.215

Hom.:

2231

Bravo

AF:

0.182

Asia WGS

AF:

0.271

AC:

940

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.4

DANN

Benign

0.64

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over