4-154733269-T-C

Variant names:

• chr4-154733269-T-C
• rs727153
• ENST00000499392.1:n.471+1483T>C

Variant summary

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

The ENST00000499392.1(LRAT):​n.471+1483T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,034 control chromosomes in the GnomAD database, including 28,007 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 0.60 (28007 hom., cov: 31)
• Consequence: LRAT ENST00000499392.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.108
• Publications: 25 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

LOC124900169 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900169	XR_007058337.1	n.3340+1483T>C		intron_variant	Intron 3 of 3
LOC124900169	XR_007058343.1	n.594+1483T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000499392.1	n.471+1483T>C		intron_variant	Intron 5 of 5	1
LRAT	ENST00000502525.5	c.-2+4486T>C		intron_variant	Intron 3 of 3	4		ENSP00000422324.1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90425 AN: 151916 Hom.: 27955 Cov.: 31

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.595 AC: 90536 AN: 152034 Hom.: 28007 Cov.: 31 AF XY: 0.608 AC XY: 45169 AN XY: 74322

African (AFR) AF: 0.737 AC: 30565 AN: 41478

American (AMR) AF: 0.660 AC: 10080 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1745 AN: 3470

East Asian (EAS) AF: 0.777 AC: 4026 AN: 5184

South Asian (SAS) AF: 0.614 AC: 2955 AN: 4816

European-Finnish (FIN) AF: 0.648 AC: 6846 AN: 10562

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32604 AN: 67932

Other (OTH) AF: 0.553 AC: 1168 AN: 2114

Alfa AF: 0.512 Hom.: 96459

Bravo AF: 0.600

Asia WGS AF: 0.712 AC: 2479 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	3.0
DANN	Benign	0.45
PhyloP100		-0.11

Splicing

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

Other links and lift over

dbSNP: rs727153; hg19: chr4-155654421;