rs193920746

Variant names:

• chr17-28633627-C-T
• rs193920746
• NM_014680.5:c.3387G>A

Variant summary

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

The NM_014680.5(BLTP2):​c.3387G>A​(p.Trp1129*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: BLTP2 NM_014680.5 stop_gained
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.51
• Publications: 0 publications found

Genes affected

BLTP2 (HGNC:28960): (bridge-like lipid transfer protein family member 2) This gene was initially characterized in human as having high expression levels in breast carcinomas and breast cancer cell lines. This gene also has increased expression in prostrate cancer cells relative to normal prostrate tissues. Expression of this gene is negatively regulated by direct binding of the microRNA miR-195 to its 3' UTR. miR-195 has been shown to modulate the invasiveness of prostrate cancer cells and xenograft metastases by downgrading expression of this gene. In mouse, the protein encoded by this gene was identified as an antigen on acute monocytic leukemia cells. In human, alternative splicing results in multiple transcript variants encoding distinct isoforms; some of these isoforms are predicted to contain an RNA pol II promoter FMP27 protein domain and a Golgi-body-localization APT1 domain. [provided by RefSeq, Apr 2017]

ENSG00000264044 (HGNC:):

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_014680.5. 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
	BLTP2	NM_014680.5	MANE Select	c.3387G>A	p.Trp1129*	stop_gained	Exon 18 of 39	NP_055495.2
	BLTP2	NM_001321560.2		c.3387G>A	p.Trp1129*	stop_gained	Exon 18 of 39	NP_001308489.1
	BLTP2	NM_001363826.1		c.2958G>A	p.Trp986*	stop_gained	Exon 17 of 38	NP_001350755.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BLTP2	ENST00000528896.7	TSL:1 MANE Select	c.3387G>A	p.Trp1129*	stop_gained	Exon 18 of 39	ENSP00000436773.2	Q14667-1
	BLTP2	ENST00000939120.1		c.3387G>A	p.Trp1129*	stop_gained	Exon 18 of 39	ENSP00000609179.1
	BLTP2	ENST00000939122.1		c.3384G>A	p.Trp1128*	stop_gained	Exon 18 of 39	ENSP00000609181.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250916 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461766 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727178

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

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.55	D
BayesDel_noAF	Pathogenic	0.55
CADD	Pathogenic	37
DANN	Uncertain	0.99
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.95	D
PhyloP100		7.5
Vest4		0.56
GERP RS		4.5
PromoterAI		0.0066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=3/197	disease causing (fs/PTC)

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: rs193920746; hg19: chr17-26960645; COSMIC: COSV66496919; COSMIC: COSV66496919;