chr4-154744337-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_004744.5(LRAT):​c.11C>T​(p.Pro4Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P4H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LRAT
NM_004744.5 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.68
Variant links:
Genes affected
LRAT (HGNC:6685): (lecithin retinol acyltransferase) The protein encoded by this gene localizes to the endoplasmic reticulum, where it catalyzes the esterification of all-trans-retinol into all-trans-retinyl ester. This reaction is an important step in vitamin A metabolism in the visual system. Mutations in this gene have been associated with early-onset severe retinal dystrophy and Leber congenital amaurosis 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1
In a topological_domain Cytoplasmic (size 193) in uniprot entity LRAT_HUMAN there are 28 pathogenic changes around while only 5 benign (85%) in NM_004744.5
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23288107).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRATNM_004744.5 linkc.11C>T p.Pro4Leu missense_variant Exon 2 of 3 ENST00000336356.4 NP_004735.2 O95237
LRATNM_001301645.2 linkc.11C>T p.Pro4Leu missense_variant Exon 2 of 3 NP_001288574.1 O95237
LRATXM_047416405.1 linkc.11C>T p.Pro4Leu missense_variant Exon 2 of 3 XP_047272361.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRATENST00000336356.4 linkc.11C>T p.Pro4Leu missense_variant Exon 2 of 3 1 NM_004744.5 ENSP00000337224.3 O95237

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461818
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727202
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.080
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.42
.;T;T
Eigen
Uncertain
0.19
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.71
D
LIST_S2
Benign
0.82
T;.;T
M_CAP
Benign
0.0085
T
MetaRNN
Benign
0.23
T;T;T
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.4
.;M;M
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-3.1
D;N;N
REVEL
Benign
0.095
Sift
Uncertain
0.0040
D;T;T
Sift4G
Benign
0.66
T;T;T
Polyphen
0.62
.;P;P
Vest4
0.50
MutPred
0.21
Loss of methylation at K2 (P = 0.0474);Loss of methylation at K2 (P = 0.0474);Loss of methylation at K2 (P = 0.0474);
MVP
0.65
MPC
0.80
ClinPred
0.98
D
GERP RS
5.2
Varity_R
0.071
gMVP
0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-155665489; API