rs201823

Variant names:

• chr4-154747733-T-C
• rs201823
• NM_004744.5:c.541-1251T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The NM_004744.5(LRAT):​c.541-1251T>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 NM_004744.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 11 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=-0.91).
• 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 rank	MANE	Protein	UniProt
LRAT	NM_004744.5	c.541-1251T>C		intron_variant	Intron 2 of 2	ENST00000336356.4	NP_004735.2
LRAT	NM_001301645.2	c.541-1251T>C		intron_variant	Intron 2 of 2		NP_001288574.1
LRAT	XM_047416405.1	c.541-456T>C		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.541-1251T>C		intron_variant	Intron 2 of 2	1	NM_004744.5	ENSP00000337224.3

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

African (AFR) AF: 0.252 AC: 10450 AN: 41498

American (AMR) AF: 0.334 AC: 5105 AN: 15288

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

East Asian (EAS) AF: 0.667 AC: 3447 AN: 5170

South Asian (SAS) AF: 0.396 AC: 1911 AN: 4820

European-Finnish (FIN) AF: 0.518 AC: 5466 AN: 10554

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

European-Non Finnish (NFE) AF: 0.368 AC: 25004 AN: 67908

Other (OTH) AF: 0.340 AC: 716 AN: 2106

Alfa AF: 0.348 Hom.: 6484

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
PhyloP100		0.012
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: rs201823; hg19: chr4-155668885;