15-73702513-G-T

Variant names:

• chr15-73702513-G-T
• rs770650860
• NM_001024736.2:c.338G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001329629.2(CD276):​c.-101G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,672 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CD276 NM_001329629.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001329629.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD276	NM_001024736.2	MANE Select	c.338G>T	p.Arg113Leu	missense	Exon 3 of 10	NP_001019907.1	Q5ZPR3-1
	CD276	NM_001329629.2		c.-101G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001316558.1	A0A0C4DGH0
	CD276	NM_001329628.2		c.338G>T	p.Arg113Leu	missense	Exon 3 of 8	NP_001316557.1	Q5ZPR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD276	ENST00000318443.10	TSL:2 MANE Select	c.338G>T	p.Arg113Leu	missense	Exon 3 of 10	ENSP00000320084.5	Q5ZPR3-1
	CD276	ENST00000564751.5	TSL:1	c.338G>T	p.Arg113Leu	missense	Exon 2 of 7	ENSP00000454940.1	Q5ZPR3-2
	CD276	ENST00000537340.6	TSL:2	c.-101G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000441087.2	A0A0C4DGH0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460672 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726744

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52382

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111934

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	0.0035	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.018
Eigen_PC	Benign	0.00046
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.57	D
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.2
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.32
Sift	Benign	0.036	D
Sift4G	Benign	0.20	T
Polyphen		0.51	P
Vest4		0.40
MutPred		0.64		Loss of methylation at R108 (P = 0.0776)
MVP		0.66
MPC		0.21
ClinPred		0.65	D
GERP RS		2.9
Varity_R		0.28
gMVP		0.39

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

Other links and lift over

dbSNP: rs770650860; hg19: chr15-73994854;