chr4-154747558-G-A

Variant names:

• chr4-154747558-G-A
• rs201824
• NM_004744.5:c.541-1426G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004744.5(LRAT):​c.541-1426G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 151,938 control chromosomes in the GnomAD database, including 9,749 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (9749 hom., cov: 32)
• Consequence: LRAT NM_004744.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• Leber congenital amaurosis 14

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Leber congenital amaurosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRAT	NM_004744.5	c.541-1426G>A		intron_variant	Intron 2 of 2	ENST00000336356.4	NP_004735.2
LRAT	NM_001301645.2	c.541-1426G>A		intron_variant	Intron 2 of 2		NP_001288574.1
LRAT	XM_047416405.1	c.541-631G>A		intron_variant	Intron 2 of 2		XP_047272361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000336356.4	c.541-1426G>A		intron_variant	Intron 2 of 2	1	NM_004744.5	ENSP00000337224.3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51939 AN: 151820 Hom.: 9750 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.334

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.342 AC: 51945 AN: 151938 Hom.: 9749 Cov.: 32 AF XY: 0.353 AC XY: 26234 AN XY: 74262

African (AFR) AF: 0.211 AC: 8764 AN: 41452

American (AMR) AF: 0.330 AC: 5048 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3470

East Asian (EAS) AF: 0.665 AC: 3431 AN: 5160

South Asian (SAS) AF: 0.395 AC: 1902 AN: 4812

European-Finnish (FIN) AF: 0.518 AC: 5459 AN: 10544

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 24960 AN: 67906

Other (OTH) AF: 0.336 AC: 710 AN: 2114

Alfa AF: 0.352 Hom.: 31849

Bravo AF: 0.323

Asia WGS AF: 0.496 AC: 1728 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.78
PhyloP100		-0.084
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs201824; hg19: chr4-155668710;