Genetic Variant BLTP2:p.Pro1514Ser (chr17-28628319-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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. 15/23 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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

Variant links:

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]

BLTP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

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 GnomAd4 at 15 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP2	NM_014680.5 link	c.4540C>T	p.Pro1514Ser	missense_variant	Exon 24 of 39	ENST00000528896.7	NP_055495.2	Q14667-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BLTP2	ENST00000528896.7 link	c.4540C>T	p.Pro1514Ser	missense_variant	Exon 24 of 39	1	NM_014680.5	ENSP00000436773.2		Q14667-1
BLTP2	ENST00000389003.7 link	c.4111C>T	p.Pro1371Ser	missense_variant	Exon 24 of 39	5		ENSP00000467716.1		K7EQ86

Frequencies

GnomAD3 genomes

AF:

0.00543

AC:

826

AN:

152152

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00488

AC:

1227

AN:

251456

AF XY:

0.00511

show subpopulations

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 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.:

Cov.:

AF XY:

0.00661

AC XY:

4810

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.00208

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.0173

AC:

452

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.000672

AC:

AN:

86256

Gnomad4 FIN exome

AF:

0.00110

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.00781

AC:

8683

AN:

1111996

Gnomad4 Remaining exome

AF:

0.00573

AC:

346

AN:

60396

Heterozygous variant carriers

511

1022

1532

2043

2554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

332

664

996

1328

1660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00542

AC:

825

AN:

152270

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

376

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00108

AC:

0.00108314

AN:

0.00108314

Gnomad4 AMR

AF:

0.00288

AC:

0.00287619

AN:

0.00287619

Gnomad4 ASJ

AF:

0.0153

AC:

0.0152738

AN:

0.0152738

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000414

AC:

0.00041425

AN:

0.00041425

Gnomad4 FIN

AF:

0.000848

AC:

0.000848096

AN:

0.000848096

Gnomad4 NFE

AF:

0.00804

AC:

0.00804175

AN:

0.00804175

Gnomad4 OTH

AF:

0.00379

AC:

0.00379147

AN:

0.00379147

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00708

Hom.:

Bravo

AF:

0.00642

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00468

AC:

568

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00851

EpiControl

AF:

0.00919

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BLTP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.55

CADD

Benign

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

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.0031

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.49

N;.;.

PrimateAI

Benign

0.34

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

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.041

gMVP

0.41

Mutation Taster

=96/4

polymorphism

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over