15-73685996-C-T

Position:

• chr15-73685996-C-T

Variant summary

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

The NM_001024736.2(CD276):​c.-55+1536C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,000 control chromosomes in the GnomAD database, including 8,346 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 0.31 (8346 hom., cov: 31)
• Consequence: CD276 NM_001024736.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.783

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD276	NM_001024736.2	c.-55+1536C>T		intron_variant		ENST00000318443.10	NP_001019907.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD276	ENST00000318443.10	c.-55+1536C>T		intron_variant		2	NM_001024736.2	ENSP00000320084.5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47331 AN: 151882 Hom.: 8344 Cov.: 31

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.329

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.312 AC: 47361 AN: 152000 Hom.: 8346 Cov.: 31 AF XY: 0.306 AC XY: 22756 AN XY: 74282

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.0267

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.325

Alfa AF: 0.378 Hom.: 19563

Bravo AF: 0.306

Asia WGS AF: 0.126 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.77

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

Other links and lift over

dbSNP: rs8038465; hg19: chr15-73978337;