chr15-73685996-C-T

Variant names:

• chr15-73685996-C-T
• rs8038465
• NM_001024736.2:c.-55+1536C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024736.2. 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.-55+1536C>T		intron	N/A	NP_001019907.1	Q5ZPR3-1
	CD276	NM_001329629.2		c.-360+1536C>T		intron	N/A	NP_001316558.1	A0A0C4DGH0
	CD276	NM_001329628.2		c.-55+1097C>T		intron	N/A	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.-55+1536C>T		intron	N/A	ENSP00000320084.5	Q5ZPR3-1
	CD276	ENST00000921507.1		c.-55+1536C>T		intron	N/A	ENSP00000591566.1
	CD276	ENST00000864253.1		c.-164+1536C>T		intron	N/A	ENSP00000534312.1

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

African (AFR) AF: 0.191 AC: 7920 AN: 41468

American (AMR) AF: 0.334 AC: 5103 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.0267 AC: 138 AN: 5170

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4820

European-Finnish (FIN) AF: 0.327 AC: 3451 AN: 10542

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.404 AC: 27473 AN: 67940

Other (OTH) AF: 0.325 AC: 688 AN: 2114

Alfa AF: 0.367 Hom.: 43957

Bravo AF: 0.306

Asia WGS AF: 0.126 AC: 444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.8
DANN	Benign	0.77
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

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: rs8038465; hg19: chr15-73978337;