Genetic Variant ENST00000538554.6:c.346-953G>C (chr11-69657605-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.465

Publications

10 publications found

Variant links:

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]

LTO1 links:

LOC124902704 (HGNC:):

LOC124902704 links:

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new If you want to explore the variant's impact on the transcript ENST00000538554.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

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

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LTO1	ENST00000538554.6	TSL:2	c.346-953G>C	intron	N/A	ENSP00000446428.3	B4DFA5
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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0767

AC XY:

13276

AN XY:

173132

show subpopulations

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:

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:

AN:

2776

European-Non Finnish (NFE)

AF:

0.102

AC:

16203

AN:

158666

Other (OTH)

AF:

0.0827

AC:

1175

AN:

14204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1636

3273

4909

6546

8182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0830

AC:

12637

AN:

152292

Hom.:

773

Cov.:

AF XY:

0.0858

AC XY:

6385

AN XY:

74452

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6871

AN:

68020

Other (OTH)

AF:

0.0597

AC:

126

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

592

1184

1776

2368

2960

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.74

PhyloP100

-0.47

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over