Genetic Variant BLTP3B:p.Glu1416Asp (chr12-100039623-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015054.2(BLTP3B):c.4248G>C(p.Glu1416Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BLTP3B
NM_015054.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.324

Publications

0 publications found

Variant links:

Genes affected

BLTP3B (HGNC:29102): (bridge-like lipid transfer protein family member 3B) Enables GARP complex binding activity and protein homodimerization activity. Located in cytosol and early endosome. [provided by Alliance of Genome Resources, Apr 2022]

BLTP3B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05507779).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015054.2. 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
	BLTP3B	NM_015054.2	MANE Select	c.4248G>C	p.Glu1416Asp	missense	Exon 20 of 21	NP_055869.1	A0JNW5-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLTP3B	ENST00000279907.12	TSL:1 MANE Select	c.4248G>C	p.Glu1416Asp	missense	Exon 20 of 21	ENSP00000279907.7	A0JNW5-1
BLTP3B	ENST00000545232.6	TSL:1	c.3198G>C	p.Glu1066Asp	missense	Exon 14 of 15	ENSP00000444824.2	A0A0C4DGH6
BLTP3B	ENST00000949295.1		c.4149G>C	p.Glu1383Asp	missense	Exon 20 of 21	ENSP00000619354.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250266

AF XY:

0.00

show subpopulations

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:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726906

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111598

Other (OTH)

AF:

0.00

AC:

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000656

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41576

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000508

Hom.:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.0

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0014

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.77

M_CAP

Benign

0.0037

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

-0.32

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.42

REVEL

Benign

0.075

Sift

Benign

0.086

Sift4G

Benign

0.29

Polyphen

0.79

Vest4

0.15

MutPred

0.092

Loss of helix (P = 0.1299)

MVP

0.043

MPC

0.11

ClinPred

0.069

GERP RS

2.0

Varity_R

0.037

gMVP

0.20

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over