11-69671823-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_153451.3(LTO1):c.157-4A>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00753 in 1,554,730 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0078 (57 hom.)
• Consequence: LTO1 NM_153451.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00003628
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.291

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-69671823-T-G is Benign according to our data. Variant chr11-69671823-T-G is described in ClinVar as [Benign]. Clinvar id is 781964.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTO1	NM_153451.3	c.157-4A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000279147.9
LTO1	XM_006718470.4	c.157-4A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTO1	ENST00000279147.9	c.157-4A>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_153451.3	P1

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 775 AN: 152074 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00347

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00660 AC: 1659 AN: 251400 Hom.: 11 AF XY: 0.00718 AC XY: 976 AN XY: 135892

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.0221

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0135

Gnomad FIN exome AF: 0.000926

Gnomad NFE exome AF: 0.00695

Gnomad OTH exome AF: 0.00847

GnomAD4 exome AF: 0.00780 AC: 10936 AN: 1402538 Hom.: 57 Cov.: 23 AF XY: 0.00796 AC XY: 5581 AN XY: 701452

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00439

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0134

Gnomad4 FIN exome AF: 0.00131

Gnomad4 NFE exome AF: 0.00789

Gnomad4 OTH exome AF: 0.00865

GnomAD4 genome AF: 0.00509 AC: 775 AN: 152192 Hom.: 3 Cov.: 32 AF XY: 0.00485 AC XY: 361 AN XY: 74402

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00347

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00995

Gnomad4 FIN AF: 0.000944

Gnomad4 NFE AF: 0.00747

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.00628 Hom.: 3

Bravo AF: 0.00511

Asia WGS AF: 0.00549 AC: 19 AN: 3478

EpiCase AF: 0.00883

EpiControl AF: 0.00794

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 03, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	8.9
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.37		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.37		Position offset: -4

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

Publications

LitVar

Other links and lift over

dbSNP: rs142367375; hg19: chr11-69486591;