11-69657605-C-G

Variant names:

• chr11-69657605-C-G
• rs11603541
• ENST00000538554.6:c.346-953G>C

Variant summary

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

The ENST00000538554.6(LTO1):​c.346-953G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.081 in 456,314 control chromosomes in the GnomAD database, including 2,113 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 0.083 (773 hom., cov: 33)
  • Exomes 𝑓: 0.080 (1340 hom.)
• Consequence: LTO1 ENST00000538554.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465
• Publications: 10 publications found

Genes affected

LTO1 (HGNC:17589): (LTO1 maturation factor of ABCE1) Involved in protein maturation by [4Fe-4S] cluster transfer; ribosomal large subunit biogenesis; and translational initiation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC124902704 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000538554.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTO1	ENST00000538554.6	TSL:2	c.346-953G>C		intron	N/A	ENSP00000446428.3
	LTO1	ENST00000542515.5	TSL:2	n.826G>C		non_coding_transcript_exon	Exon 1 of 3
	LTO1	ENST00000569105.5	TSL:2	n.270-953G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12635 AN: 152174 Hom.: 774 Cov.: 33

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0339

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0584

GnomAD2 exomes AF: 0.0657 AC: 8830 AN: 134400 AF XY: 0.0653

Gnomad AFR exome AF: 0.0503

Gnomad AMR exome AF: 0.0215

Gnomad ASJ exome AF: 0.0500

Gnomad EAS exome AF: 0.00162

Gnomad FIN exome AF: 0.234

Gnomad NFE exome AF: 0.0969

Gnomad OTH exome AF: 0.0676

GnomAD4 exome AF: 0.0800 AC: 24311 AN: 304022 Hom.: 1340 Cov.: 0 AF XY: 0.0767 AC XY: 13276 AN XY: 173132

African (AFR) AF: 0.0484 AC: 417 AN: 8616

American (AMR) AF: 0.0211 AC: 574 AN: 27268

Ashkenazi Jewish (ASJ) AF: 0.0513 AC: 553 AN: 10780

East Asian (EAS) AF: 0.00185 AC: 17 AN: 9202

South Asian (SAS) AF: 0.0392 AC: 2343 AN: 59728

European-Finnish (FIN) AF: 0.231 AC: 2952 AN: 12782

Middle Eastern (MID) AF: 0.0277 AC: 77 AN: 2776

European-Non Finnish (NFE) AF: 0.102 AC: 16203 AN: 158666

Other (OTH) AF: 0.0827 AC: 1175 AN: 14204

GnomAD4 genome AF: 0.0830 AC: 12637 AN: 152292 Hom.: 773 Cov.: 33 AF XY: 0.0858 AC XY: 6385 AN XY: 74452

African (AFR) AF: 0.0517 AC: 2150 AN: 41574

American (AMR) AF: 0.0338 AC: 518 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 179 AN: 3472

East Asian (EAS) AF: 0.00348 AC: 18 AN: 5172

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4830

European-Finnish (FIN) AF: 0.241 AC: 2553 AN: 10600

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6871 AN: 68020

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0646 Hom.: 110

Bravo AF: 0.0650

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.74
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs11603541; hg19: chr11-69472373;