Variant 9-5462876-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014143.4(CD274):c.437C>G(p.Pro146Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 1,613,860 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P146T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0035 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 15 hom. )

Consequence

CD274
NM_014143.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.835

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062650144).

BP6

Variant 9-5462876-C-G is Benign according to our data. Variant chr9-5462876-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2659049.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD274	NM_014143.4 linkuse as main transcript	c.437C>G	p.Pro146Arg	missense_variant	4/7	ENST00000381577.4
LOC124902114	XR_007061406.1 linkuse as main transcript	n.256-3689G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD274	ENST00000381577.4 linkuse as main transcript	c.437C>G	p.Pro146Arg	missense_variant	4/7	1	NM_014143.4	P1	Q9NZQ7-1
	ENST00000661858.1 linkuse as main transcript	n.277-3689G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

540

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00462

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00393

AC:

988

AN:

251104

Hom.:

AF XY:

0.00393

AC XY:

534

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00420

Gnomad ASJ exome

AF:

0.0165

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00185

Gnomad NFE exome

AF:

0.00512

Gnomad OTH exome

AF:

0.00637

GnomAD4 exome

AF:

0.00412

AC:

6017

AN:

1461582

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

2964

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.000658

Gnomad4 AMR exome

AF:

0.00474

Gnomad4 ASJ exome

AF:

0.0163

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.00445

Gnomad4 OTH exome

AF:

0.00442

GnomAD4 genome

AF:

0.00355

AC:

540

AN:

152278

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00462

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00375

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00367

AC:

446

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

CD274: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

.;D

Eigen

Benign

0.042

Eigen_PC

Benign

-0.029

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.0063

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Pathogenic

3.1

.;M

MutationTaster

Benign

0.95

D;D

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.81

.;P

Vest4

0.14

MVP

0.49

MPC

1.2

ClinPred

0.10

GERP RS

4.0

Varity_R

0.37

gMVP

0.34

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