rs1074801

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XR_007058346.1(LOC124900169):​n.499-17100A>C variant causes a intron, non coding transcript 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: LOC124900169 XR_007058346.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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]

LOC124900169 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
LOC124900169	XR_007058346.1	n.499-17100A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000499392.1	n.146+18736A>C		intron_variant, non_coding_transcript_variant		1
LRAT	ENST00000502525.5	c.-83+18736A>C		intron_variant		4		ENSP00000422324
LRAT	ENST00000500890.6	n.273+18736A>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.687

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.814

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.596

Alfa AF: 0.551 Hom.: 43901

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1074801; hg19: chr4-155576284;