Variant 11-69671823-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153451.3(LTO1):c.157-4A>C variant causes a splice region, 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, intron

Scores

Splicing: ADA: 0.00003628

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.291

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 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_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTO1	NM_153451.3 link	c.157-4A>C		splice_region_variant, intron_variant	Intron 2 of 4	ENST00000279147.9	NP_703152.1	Q8WV07A0A024R5H3
LTO1	XM_006718470.4 link	c.157-4A>C		splice_region_variant, intron_variant	Intron 2 of 5		XP_006718533.1	Q8WV07A0A024R5H3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTO1	ENST00000279147.9 link	c.157-4A>C		splice_region_variant, intron_variant	Intron 2 of 4	1	NM_153451.3	ENSP00000279147.5		Q8WV07
LTO1	ENST00000538554.6 link	c.157-4A>C		splice_region_variant, intron_variant	Intron 2 of 6	2		ENSP00000446428.3		B4DFA5

Frequencies

GnomAD3 genomes

AF:

0.00510

AC:

775

AN:

152074

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00718

AC XY:

976

AN XY:

135892

show subpopulations

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.:

Cov.:

AF XY:

0.00796

AC XY:

5581

AN XY:

701452

show subpopulations

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.:

Cov.:

AF XY:

0.00485

AC XY:

361

AN XY:

74402

show subpopulations

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.:

Bravo

AF:

0.00511

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00883

EpiControl

AF:

0.00794

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 03, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over