Genetic Variant LRAT:p.Ser175Ser (chr4-154744851-T-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_004744.5(LRAT):c.525T>C(p.Ser175Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000806 in 1,613,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

LRAT
NM_004744.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.70

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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 4-154744851-T-C is Benign according to our data. Variant chr4-154744851-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1078570.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000988 (15/151876) while in subpopulation NFE AF= 0.000191 (13/67950). AF 95% confidence interval is 0.000112. There are 0 homozygotes in gnomad4. There are 6 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRAT	NM_004744.5 link	c.525T>C	p.Ser175Ser	synonymous_variant	Exon 2 of 3	ENST00000336356.4	NP_004735.2	O95237
LRAT	NM_001301645.2 link	c.525T>C	p.Ser175Ser	synonymous_variant	Exon 2 of 3		NP_001288574.1	O95237
LRAT	XM_047416405.1 link	c.525T>C	p.Ser175Ser	synonymous_variant	Exon 2 of 3		XP_047272361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRAT	ENST00000336356.4 link	c.525T>C	p.Ser175Ser	synonymous_variant	Exon 2 of 3	1	NM_004744.5	ENSP00000337224.3	O95237
LRAT	ENST00000507827.5 link	c.525T>C	p.Ser175Ser	synonymous_variant	Exon 2 of 3	1		ENSP00000426761.1	O95237
LRAT	ENST00000510733.1 link	n.852T>C		non_coding_transcript_exon_variant	Exon 1 of 2	1
LRAT	ENST00000499392.1 link	n.472-3338T>C		intron_variant	Intron 5 of 5	1

Frequencies

GnomAD3 genomes

AF:

0.0000988

AC:

AN:

151876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000564

AC:

AN:

248264

Hom.:

AF XY:

0.0000446

AC XY:

AN XY:

134666

show subpopulations

Gnomad AFR exome

AF:

0.0000620

Gnomad AMR exome

AF:

0.00

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:

0.000108

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1461278

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

726936

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.0000980

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000988

AC:

AN:

151876

Hom.:

Cov.:

AF XY:

0.0000809

AC XY:

AN XY:

74184

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000907

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 18, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.51

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