Variant chr9-5470497-A-G 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.*2635A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 214,568 control chromosomes in the GnomAD database, including 7,599 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4763 hom., cov: 32)

Exomes 𝑓: 0.28 ( 2836 hom. )

Consequence

CD274
NM_014143.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.165

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=-0.81).

BP6

Variant 9-5470497-A-G is Benign according to our data. Variant chr9-5470497-A-G is described in ClinVar as [Benign]. Clinvar id is 1251890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD274	NM_014143.4 linkuse as main transcript	c.*2635A>G		3_prime_UTR_variant	7/7	ENST00000381577.4
LOC124902114	XR_007061406.1 linkuse as main transcript	n.256-11310T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD274	ENST00000381577.4 linkuse as main transcript	c.*2635A>G	3_prime_UTR_variant	7/7	1	NM_014143.4	P1	Q9NZQ7-1
	ENST00000661858.1 linkuse as main transcript	n.277-11310T>C	intron_variant, non_coding_transcript_variant
CD274	ENST00000381573.8 linkuse as main transcript	c.*2635A>G	3_prime_UTR_variant	6/6	5			Q9NZQ7-2

Frequencies

GnomAD3 genomes

AF:

0.233

AC:

35356

AN:

151984

Hom.:

4758

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.271

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.233

GnomAD4 exome

AF:

0.278

AC:

17367

AN:

62466

Hom.:

2836

Cov.:

AF XY:

0.278

AC XY:

8026

AN XY:

28868

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.337

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.512

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.245

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.233

AC:

35372

AN:

152102

Hom.:

4763

Cov.:

AF XY:

0.236

AC XY:

17579

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.131

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.536

Gnomad4 SAS

AF:

0.206

Gnomad4 FIN

AF:

0.233

Gnomad4 NFE

AF:

0.247

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.217

Hom.:

549

Bravo

AF:

0.239

Asia WGS

AF:

0.297

AC:

1032

AN:

3476

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.81

CADD

Benign

4.1

DANN

Benign

0.82

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over