rs10004545

Positions:

• chr4-154726938-A-G
• chr4-154726938-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000499392.1(LRAT):​n.147-1765A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 152,012 control chromosomes in the GnomAD database, including 17,170 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 0.46 (17170 hom., cov: 32)
• Consequence: LRAT ENST00000499392.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

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]

LOC124900169 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124900169	XR_007058337.1	n.257-1765A>G		intron_variant, non_coding_transcript_variant
LOC124900169	XR_007058343.1	n.257-1765A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRAT	ENST00000499392.1	n.147-1765A>G		intron_variant, non_coding_transcript_variant		1
LRAT	ENST00000502525.5	c.-82-1765A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70290 AN: 151894 Hom.: 17145 Cov.: 32

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.421

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

GnomAD4 genome AF: 0.463 AC: 70347 AN: 152012 Hom.: 17170 Cov.: 32 AF XY: 0.470 AC XY: 34917 AN XY: 74302

Gnomad4 AFR AF: 0.583

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.424

Alfa AF: 0.440 Hom.: 2428

Bravo AF: 0.460

Asia WGS AF: 0.567 AC: 1972 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.1
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10004545; hg19: chr4-155648090;