rs75368761

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_004744.5(LRAT):c.74T>A(p.Phe25Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,094 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0070 ( 17 hom., cov: 31)

Exomes 𝑓: 0.00065 ( 12 hom. )

Consequence

LRAT
NM_004744.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 1.92

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]

LRAT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a chain Lecithin retinol acyltransferase (size 229) in uniprot entity LRAT_HUMAN there are 15 pathogenic changes around while only 3 benign (83%) in NM_004744.5

BP4

Computational evidence support a benign effect (MetaRNN=0.0054549873).

BP6

Variant 4-154744400-T-A is Benign according to our data. Variant chr4-154744400-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 100574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-154744400-T-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00697 (1061/152216) while in subpopulation AFR AF= 0.0247 (1028/41548). AF 95% confidence interval is 0.0235. There are 17 homozygotes in gnomad4. There are 491 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRAT	NM_004744.5 link	c.74T>A	p.Phe25Tyr	missense_variant	Exon 2 of 3	ENST00000336356.4	NP_004735.2	O95237
LRAT	NM_001301645.2 link	c.74T>A	p.Phe25Tyr	missense_variant	Exon 2 of 3		NP_001288574.1	O95237
LRAT	XM_047416405.1 link	c.74T>A	p.Phe25Tyr	missense_variant	Exon 2 of 3		XP_047272361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000336356.4 link	c.74T>A	p.Phe25Tyr	missense_variant	Exon 2 of 3	1	NM_004744.5	ENSP00000337224.3		O95237

Frequencies

GnomAD3 genomes

AF:

0.00696

AC:

1059

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00169

AC:

424

AN:

251436

Hom.:

AF XY:

0.000986

AC XY:

134

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.0251

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000646

AC:

944

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000547

AC XY:

398

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.000537

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:

0.00000809

Gnomad4 OTH exome

AF:

0.000944

GnomAD4 genome

AF:

0.00697

AC:

1061

AN:

152216

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

491

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0247

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00766

ESP6500AA

AF:

0.0284

AC:

125

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00229

AC:

278

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Sep 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 10, 2021

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Leber congenital amaurosis 14

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Retinitis pigmentosa

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

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

0.16

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.47

.;T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.58

T;.;T

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

.;M;M

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.20

T;D;D

Sift4G

Benign

0.20

T;T;T

Polyphen

0.96

.;D;D

Vest4

0.14

MVP

0.40

MPC

0.70

ClinPred

0.047

GERP RS

5.0

Varity_R

0.24

gMVP

0.64

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

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