dbSNP rs11603541: LTO1: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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124902704	XM_047427985.1 link	c.311G>C	p.Trp104Ser	missense_variant	Exon 1 of 1		XP_047283941.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
LTO1	ENST00000538554.6 link	c.346-953G>C	intron_variant	Intron 4 of 6	2	ENSP00000446428.3
LTO1	ENST00000542515.5 link	n.826G>C	non_coding_transcript_exon_variant	Exon 1 of 3	2
LTO1	ENST00000569105.5 link	n.270-953G>C	intron_variant	Intron 3 of 5	2

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 v4.3

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over