Genetic Variant BLTP1:p.Arg147Ser (chr4-122186116-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001384125.1(BLTP1):c.439C>A(p.Arg147Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R147C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

BLTP1
NM_001384125.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.70

Publications

2 publications found

Variant links:

Genes affected

BLTP1 (HGNC:26953): (bridge-like lipid transfer protein family member 1) This gene is located on the long arm of chromosome 4 in a region that is associated with susceptibility to celiac disease. The encoded protein is similar to a Chinese hamster protein that is associated with spermatocyte and adipocyte differentiation. The C-terminus of the protein is also similar to a Caenorhabditis elegans protein that plays a role in lipid storage. In mammals, this protein is thought to function in the regulation of epithelial growth and differentiation, and in tumor development. [provided by RefSeq, Oct 2009]

BLTP1 Gene-Disease associations (from GenCC):

Alkuraya-Kucinskas syndrome
Inheritance: AR Classification: STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

BLTP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22070256).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384125.1. 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
	BLTP1	NM_001384125.1	MANE Select	c.439C>A	p.Arg147Ser	missense	Exon 7 of 88	NP_001371054.1	A0A7P0T938
	BLTP1	NM_015312.4		c.439C>A	p.Arg147Ser	missense	Exon 5 of 84	NP_056127.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BLTP1	ENST00000679879.1	MANE Select	c.439C>A	p.Arg147Ser	missense	Exon 7 of 88	ENSP00000505357.1	A0A7P0T938
BLTP1	ENST00000388738.8	TSL:1	c.439C>A	p.Arg147Ser	missense	Exon 7 of 85	ENSP00000373390.4	A0A8J8Z0T9
BLTP1	ENST00000264501.8	TSL:5	c.439C>A	p.Arg147Ser	missense	Exon 7 of 86	ENSP00000264501.4	Q2LD37-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248566

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000828

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.034

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.053

MetaRNN

Benign

0.22

MetaSVM

Uncertain

-0.045

MutationAssessor

Benign

0.81

PhyloP100

7.7

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.2

REVEL

Benign

0.27

Sift

Benign

0.044

Sift4G

Uncertain

0.012

Polyphen

0.0060

Vest4

0.47

MutPred

0.33

Loss of stability (P = 0.0978)

MVP

0.61

MPC

0.63

ClinPred

0.88

GERP RS

4.9

Varity_R

0.26

gMVP

0.36

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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