Genetic Variant BLTP3B:p.Ile1175Val (chr12-100051123-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015054.2(BLTP3B):c.3523A>G(p.Ile1175Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,614,088 control chromosomes in the GnomAD database, including 217 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 Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.021 ( 112 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 105 hom. )

Consequence

BLTP3B
NM_015054.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.209

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012082756).

BP6

Variant 12-100051123-T-C is Benign according to our data. Variant chr12-100051123-T-C is described in ClinVar as [Benign]. Clinvar id is 784307.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BLTP3B	NM_015054.2 link	c.3523A>G	p.Ile1175Val	missense_variant	Exon 16 of 21	ENST00000279907.12	NP_055869.1	A0JNW5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BLTP3B	ENST00000279907.12 link	c.3523A>G	p.Ile1175Val	missense_variant	Exon 16 of 21	1	NM_015054.2	ENSP00000279907.7	A0JNW5-1
BLTP3B	ENST00000545232.6 link	c.2473A>G	p.Ile825Val	missense_variant	Exon 10 of 15	1		ENSP00000444824.2	A0A0C4DGH6
BLTP3B	ENST00000547504.1 link	n.752A>G		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0205

AC:

3124

AN:

152210

Hom.:

112

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0708

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00936

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00541

AC:

1359

AN:

251324

Hom.:

AF XY:

0.00387

AC XY:

526

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.00472

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000194

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00222

AC:

3252

AN:

1461760

Hom.:

105

Cov.:

AF XY:

0.00193

AC XY:

1400

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0743

Gnomad4 AMR exome

AF:

0.00528

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000220

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.00527

GnomAD4 genome

AF:

0.0206

AC:

3140

AN:

152328

Hom.:

112

Cov.:

AF XY:

0.0200

AC XY:

1486

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.00935

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00331

Hom.:

Bravo

AF:

0.0237

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0624

AC:

275

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00664

AC:

806

Asia WGS

AF:

0.00664

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.4

DANN

Benign

0.45

DEOGEN2

Benign

0.00029

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.43

N;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.040

N;N

REVEL

Benign

0.034

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0010

B;.

Vest4

0.060

MVP

0.043

MPC

0.097

ClinPred

0.00098

GERP RS

-1.9

Varity_R

0.014

gMVP

0.072

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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