rs12501328

Variant names:

• chr4-154741179-A-G
• rs12501328
• ENST00000507827.5:c.-2+281A>G

Variant summary

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

The ENST00000507827.5(LRAT):​c.-2+281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 131,240 control chromosomes in the GnomAD database, including 1,680 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 0.15 (1680 hom., cov: 27)
• Consequence: LRAT ENST00000507827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 9 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

ENSG00000294315 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRAT	NM_001301645.2	c.-2+281A>G		intron_variant	Intron 1 of 2		NP_001288574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000507827.5	c.-2+281A>G		intron_variant	Intron 1 of 2	1		ENSP00000426761.1
LRAT	ENST00000499392.1	n.472-7010A>G		intron_variant	Intron 5 of 5	1
LRAT	ENST00000502525.5	c.-1-3147A>G		intron_variant	Intron 3 of 3	4		ENSP00000422324.1
ENSG00000294315	ENST00000722706.1	n.156-80A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.149 AC: 19559 AN: 131146 Hom.: 1662 Cov.: 27

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.0935

Gnomad EAS AF: 0.0420

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0959

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.149 AC: 19610 AN: 131240 Hom.: 1680 Cov.: 27 AF XY: 0.158 AC XY: 9896 AN XY: 62606

African (AFR) AF: 0.182 AC: 6443 AN: 35388

American (AMR) AF: 0.319 AC: 4046 AN: 12684

Ashkenazi Jewish (ASJ) AF: 0.0935 AC: 304 AN: 3250

East Asian (EAS) AF: 0.0415 AC: 150 AN: 3616

South Asian (SAS) AF: 0.229 AC: 859 AN: 3758

European-Finnish (FIN) AF: 0.198 AC: 1424 AN: 7184

Middle Eastern (MID) AF: 0.192 AC: 45 AN: 234

European-Non Finnish (NFE) AF: 0.0959 AC: 5993 AN: 62498

Other (OTH) AF: 0.149 AC: 267 AN: 1790

Alfa AF: 0.103 Hom.: 521

Bravo AF: 0.142

Asia WGS AF: 0.143 AC: 499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.33
PhyloP100		-0.23
PromoterAI		-0.0081	Neutral
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: rs12501328; hg19: chr4-155662331;