chr15-73713259-C-T

Variant names:

• chr15-73713259-C-T
• rs3816661
• NM_001024736.2:c.*303C>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.*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
• Publications: 16 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.45 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD276	NM_001024736.2	MANE Select	c.*303C>T		3_prime_UTR	Exon 10 of 10	NP_001019907.1
	CD276	NM_001329629.2		c.*303C>T		3_prime_UTR	Exon 9 of 9	NP_001316558.1
	CD276	NM_001329628.2		c.*303C>T		3_prime_UTR	Exon 8 of 8	NP_001316557.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD276	ENST00000318443.10	TSL:2 MANE Select	c.*303C>T		3_prime_UTR	Exon 10 of 10	ENSP00000320084.5
	CD276	ENST00000559465.1	TSL:1	n.365C>T		non_coding_transcript_exon	Exon 2 of 2
	CD276	ENST00000559073.1	TSL:1	n.*108-31C>T		intron	N/A	ENSP00000453842.1

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

African (AFR) AF: 0.411 AC: 2728 AN: 6632

American (AMR) AF: 0.469 AC: 3630 AN: 7740

Ashkenazi Jewish (ASJ) AF: 0.389 AC: 3350 AN: 8614

East Asian (EAS) AF: 0.442 AC: 6983 AN: 15812

South Asian (SAS) AF: 0.366 AC: 7437 AN: 20326

European-Finnish (FIN) AF: 0.397 AC: 7216 AN: 18160

Middle Eastern (MID) AF: 0.415 AC: 517 AN: 1246

European-Non Finnish (NFE) AF: 0.461 AC: 74089 AN: 160580

Other (OTH) AF: 0.440 AC: 7028 AN: 15984

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

African (AFR) AF: 0.407 AC: 16885 AN: 41452

American (AMR) AF: 0.458 AC: 6998 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1341 AN: 3472

East Asian (EAS) AF: 0.358 AC: 1842 AN: 5152

South Asian (SAS) AF: 0.342 AC: 1641 AN: 4802

European-Finnish (FIN) AF: 0.375 AC: 3961 AN: 10576

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30841 AN: 67968

Other (OTH) AF: 0.427 AC: 901 AN: 2108

Alfa AF: 0.436 Hom.: 25306

Bravo AF: 0.433

Asia WGS AF: 0.343 AC: 1193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.4
DANN	Benign	0.49
PhyloP100		-0.036
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3816661; hg19: chr15-74005600;