Genetic Variant CD276:p.Val429Met (chr15-73704388-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001024736.2(CD276):c.1285G>A(p.Val429Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00454 in 1,614,118 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0047 ( 17 hom. )

Consequence

CD276
NM_001024736.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.397

Publications

5 publications found

Variant links:

Genes affected

CD276 (HGNC:19137): (CD276 molecule) The protein encoded by this gene belongs to the immunoglobulin superfamily, and thought to participate in the regulation of T-cell-mediated immune response. Studies show that while the transcript of this gene is ubiquitously expressed in normal tissues and solid tumors, the protein is preferentially expressed only in tumor tissues. Additionally, it was observed that the 3' UTR of this transcript contains a target site for miR29 microRNA, and there is an inverse correlation between the expression of this protein and miR29 levels, suggesting regulation of expression of this gene product by miR29. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

CD276 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010781288).

BS2

High Homozygotes in GnomAdExome4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD276	NM_001024736.2 link	c.1285G>A	p.Val429Met	missense_variant	Exon 6 of 10	ENST00000318443.10	NP_001019907.1	Q5ZPR3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD276	ENST00000318443.10 link	c.1285G>A	p.Val429Met	missense_variant	Exon 6 of 10	2	NM_001024736.2	ENSP00000320084.5		Q5ZPR3-1

Frequencies

GnomAD3 genomes

AF:

0.00288

AC:

439

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000892

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00217

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00268

AC:

672

AN:

251094

AF XY:

0.00278

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00487

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00213

Gnomad NFE exome

AF:

0.00429

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00471

AC:

6886

AN:

1461760

Hom.:

Cov.:

AF XY:

0.00450

AC XY:

3273

AN XY:

727196

show subpopulations

African (AFR)

AF:

0.000418

AC:

AN:

33480

American (AMR)

AF:

0.00136

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00486

AC:

127

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000255

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00204

AC:

109

AN:

53320

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.00567

AC:

6301

AN:

1112012

Other (OTH)

AF:

0.00414

AC:

250

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

529

1057

1586

2114

2643

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

244

488

732

976

1220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00288

AC:

439

AN:

152358

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41584

American (AMR)

AF:

0.00163

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00217

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00478

AC:

325

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00289

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.000910

AC:

ESP6500EA

AF:

0.00547

AC:

ExAC

AF:

0.00254

AC:

309

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00474

EpiControl

AF:

0.00480

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.042

T;T;.;.;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.80

T;T;T;T;.

M_CAP

Benign

0.038

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.51

N;.;.;N;.

PhyloP100

0.40

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.12

N;N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.23

T;T;T;T;T

Sift4G

Uncertain

0.025

D;D;D;D;D

Polyphen

0.0060

B;.;B;B;B

Vest4

0.35

MVP

0.58

MPC

0.14

ClinPred

0.013

GERP RS

2.0

PromoterAI

-0.021

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.033

gMVP

0.26

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over