NM_004744.5:c.-199G>A

Variant names:

• chr4-154744025-G-A
• rs77224348
• NM_004744.5:c.-199G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004744.5(LRAT):​c.-199G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000353 in 283,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: LRAT NM_004744.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.389

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRAT	NM_004744.5	c.-199G>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000336356.4	NP_004735.2
LRAT	XM_047416405.1	c.-199G>A		5_prime_UTR_variant	Exon 1 of 3		XP_047272361.1
LRAT	NM_001301645.2	c.-1-301G>A		intron_variant	Intron 1 of 2		NP_001288574.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRAT	ENST00000336356	c.-199G>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_004744.5	ENSP00000337224.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000353 AC: 1 AN: 283396 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 148284

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000823

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	3.8
DANN	Benign	0.93

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

Publications

LitVar

Other links and lift over

dbSNP: rs77224348; hg19: chr4-155665177;