17-28628319-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_014680.5(BLTP2):c.4540C>T(p.Pro1514Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 1,614,142 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (15 hom., cov: 32)
  • Exomes 𝑓: 0.0067 (42 hom.)
• Consequence: BLTP2 NM_014680.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, BLTP2
• BP4: Computational evidence support a benign effect (MetaRNN=0.0030865073).
• BP6: Variant 17-28628319-G-A is Benign according to our data. Variant chr17-28628319-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647592.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLTP2	NM_014680.5	c.4540C>T	p.Pro1514Ser	missense_variant	24/39	ENST00000528896.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLTP2	ENST00000528896.7	c.4540C>T	p.Pro1514Ser	missense_variant	24/39	1	NM_014680.5	P1
BLTP2	ENST00000389003.7	c.4111C>T	p.Pro1371Ser	missense_variant	24/39	5

Frequencies

GnomAD3 genomes AF: 0.00543 AC: 826 AN: 152152 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.000848

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00804

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00488 AC: 1227 AN: 251456 Hom.: 4 AF XY: 0.00511 AC XY: 694 AN XY: 135902

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.0167

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000849

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00790

Gnomad OTH exome AF: 0.00423

GnomAD4 exome AF: 0.00668 AC: 9764 AN: 1461872 Hom.: 42 Cov.: 32 AF XY: 0.00661 AC XY: 4810 AN XY: 727236

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.00208

Gnomad4 ASJ exome AF: 0.0173

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000672

Gnomad4 FIN exome AF: 0.00110

Gnomad4 NFE exome AF: 0.00781

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.00542 AC: 825 AN: 152270 Hom.: 15 Cov.: 32 AF XY: 0.00505 AC XY: 376 AN XY: 74454

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00288

Gnomad4 ASJ AF: 0.0153

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.000848

Gnomad4 NFE AF: 0.00804

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00767 Hom.: 8

Bravo AF: 0.00642

TwinsUK AF: 0.00917 AC: 34

ALSPAC AF: 0.00701 AC: 27

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00756 AC: 65

ExAC AF: 0.00468 AC: 568

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00851

EpiControl AF: 0.00919

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

BLTP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0037	T;T;T
Eigen	Benign	-0.12
Eigen_PC	Benign	0.027
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.0031	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N;.;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.043
Sift	Benign	0.091	T;T;.
Sift4G	Benign	0.33	T;T;T
Polyphen		0.16	B;.;.
Vest4		0.19
MVP		0.44
MPC		0.21
ClinPred		0.022	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.041
gMVP		0.41

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: rs61743603; hg19: chr17-26955337;