rs201823

Positions:

• chr4-154747733-T-C
• chr4-154747733-T-G

Variant summary

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

The ENST00000336356.4(LRAT):​c.541-1251T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,018 control chromosomes in the GnomAD database, including 10,178 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 0.35 (10178 hom., cov: 33)
• Consequence: LRAT ENST00000336356.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRAT	NM_004744.5	c.541-1251T>C		intron_variant		ENST00000336356.4	NP_004735.2
LRAT	NM_001301645.2	c.541-1251T>C		intron_variant			NP_001288574.1
LRAT	XM_047416405.1	c.541-456T>C		intron_variant			XP_047272361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000336356.4	c.541-1251T>C		intron_variant		1	NM_004744.5	ENSP00000337224	P1

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53755 AN: 151900 Hom.: 10177 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.354 AC: 53770 AN: 152018 Hom.: 10178 Cov.: 33 AF XY: 0.364 AC XY: 27076 AN XY: 74288

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.334

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.368

Gnomad4 OTH AF: 0.340

Alfa AF: 0.339 Hom.: 4095

Bravo AF: 0.336

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.70

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

Other links and lift over

dbSNP: rs201823; hg19: chr4-155668885;