17-28628337-T-C

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.4522A>G(p.Thr1508Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00856 in 1,614,200 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0075 (20 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (87 hom.)
• Consequence: BLTP2 NM_014680.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0220

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=0.0032013953).
• BP6: Variant 17-28628337-T-C is Benign according to our data. Variant chr17-28628337-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2647593.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BLTP2	NM_014680.5	c.4522A>G	p.Thr1508Ala	missense_variant	24/39	ENST00000528896.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BLTP2	ENST00000528896.7	c.4522A>G	p.Thr1508Ala	missense_variant	24/39	1	NM_014680.5	P1
BLTP2	ENST00000389003.7	c.4093A>G	p.Thr1365Ala	missense_variant	24/39	5

Frequencies

GnomAD3 genomes AF: 0.00752 AC: 1144 AN: 152198 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00773

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00830 AC: 2087 AN: 251474 Hom.: 26 AF XY: 0.00817 AC XY: 1111 AN XY: 135918

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00121

Gnomad ASJ exome AF: 0.00665

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.0421

Gnomad NFE exome AF: 0.00862

Gnomad OTH exome AF: 0.00765

GnomAD4 exome AF: 0.00867 AC: 12677 AN: 1461884 Hom.: 87 Cov.: 32 AF XY: 0.00836 AC XY: 6080 AN XY: 727242

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00639

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000197

Gnomad4 FIN exome AF: 0.0409

Gnomad4 NFE exome AF: 0.00878

Gnomad4 OTH exome AF: 0.00704

GnomAD4 genome AF: 0.00751 AC: 1144 AN: 152316 Hom.: 20 Cov.: 32 AF XY: 0.00869 AC XY: 647 AN XY: 74476

Gnomad4 AFR AF: 0.00130

Gnomad4 AMR AF: 0.00287

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0467

Gnomad4 NFE AF: 0.00773

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00701 Hom.: 5

Bravo AF: 0.00454

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00796 AC: 967

EpiCase AF: 0.00687

EpiControl AF: 0.00640

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

Apr 01, 2023

BLTP2: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	1.9
Dann	Benign	0.51
DEOGEN2	Benign	0.0041	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.47	T;T;T
MetaRNN	Benign	0.0032	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N;N;.
REVEL	Benign	0.032
Sift	Benign	0.56	T;T;.
Sift4G	Benign	0.39	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.047
MVP		0.17
MPC		0.20
ClinPred		0.0016	T
GERP RS		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.25

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: rs117706969; hg19: chr17-26955355;