chr4-154655132-A-C

Variant names:

• chr4-154655132-A-C
• rs1074801
• ENST00000499392.1:n.146+18736A>C

Variant summary

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

The ENST00000502525.5(LRAT):​c.-83+18736A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,048 control chromosomes in the GnomAD database, including 32,370 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 0.64 (32370 hom., cov: 32)
• Consequence: LRAT ENST00000502525.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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: Ambry Genetics, G2P, 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000502525.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRAT	ENST00000499392.1	TSL:1	n.146+18736A>C		intron	N/A
	LRAT	ENST00000502525.5	TSL:4	c.-83+18736A>C		intron	N/A	ENSP00000422324.1	D6RC94
	LRAT	ENST00000500890.6	TSL:2	n.273+18736A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97314 AN: 151930 Hom.: 32331 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.641 AC: 97418 AN: 152048 Hom.: 32370 Cov.: 32 AF XY: 0.647 AC XY: 48127 AN XY: 74328

African (AFR) AF: 0.799 AC: 33178 AN: 41504

American (AMR) AF: 0.687 AC: 10491 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2121 AN: 3470

East Asian (EAS) AF: 0.814 AC: 4199 AN: 5156

South Asian (SAS) AF: 0.661 AC: 3183 AN: 4812

European-Finnish (FIN) AF: 0.598 AC: 6311 AN: 10552

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 36031 AN: 67966

Other (OTH) AF: 0.596 AC: 1258 AN: 2110

Alfa AF: 0.573 Hom.: 75080

Bravo AF: 0.654

Asia WGS AF: 0.763 AC: 2656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.10
DANN	Benign	0.47
PhyloP100		-1.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1074801;

hg19: chr4-155576284;