rs1074801

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr4-154655132-A-C
• chr4-154655132-A-T

Variant summary

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

The ENST00000499392.1(LRAT):​n.146+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 ENST00000499392.1 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: 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124900169	XR_007058337.1	n.256+18736A>C		intron_variant	Intron 2 of 3
LOC124900169	XR_007058338.1	n.257-17100A>C		intron_variant	Intron 2 of 5
LOC124900169	XR_007058339.1	n.257-17100A>C		intron_variant	Intron 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000499392.1	n.146+18736A>C		intron_variant	Intron 2 of 5	1
LRAT	ENST00000502525.5	c.-83+18736A>C		intron_variant	Intron 2 of 3	4		ENSP00000422324.1
LRAT	ENST00000500890.6	n.273+18736A>C		intron_variant	Intron 2 of 2	2

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 v4.3

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

Other links and lift over

dbSNP: rs1074801; hg19: chr4-155576284;