15-73713259-C-T

Variant names:

• chr15-73713259-C-T
• rs3816661
• NM_001024736.2:c.*303C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001024736.2(CD276):​c.*303C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 407,098 control chromosomes in the GnomAD database, including 39,069 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 0.43 (14019 hom., cov: 32)
  • Exomes 𝑓: 0.44 (25050 hom.)
• Consequence: CD276 NM_001024736.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD276	NM_001024736.2	c.*303C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000318443.10	NP_001019907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD276	ENST00000318443.10	c.*303C>T		3_prime_UTR_variant	Exon 10 of 10	2	NM_001024736.2	ENSP00000320084.5

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64822 AN: 151886 Hom.: 14007 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.428

GnomAD4 exome AF: 0.443 AC: 112978 AN: 255094 Hom.: 25050 Cov.: 0 AF XY: 0.438 AC XY: 57670 AN XY: 131550

Gnomad4 AFR exome AF: 0.411

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.440

GnomAD4 genome AF: 0.427 AC: 64883 AN: 152004 Hom.: 14019 Cov.: 32 AF XY: 0.423 AC XY: 31415 AN XY: 74302

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.358

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.375

Gnomad4 NFE AF: 0.454

Gnomad4 OTH AF: 0.427

Alfa AF: 0.434 Hom.: 15595

Bravo AF: 0.433

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.4
DANN	Benign	0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs3816661; hg19: chr15-74005600;