chr11-69671823-T-G

Variant names:

• chr11-69671823-T-G
• rs142367375
• NM_153451.3:c.157-4A>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

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 Likely 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/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.291
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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/Likely_benign. ClinVar VariationId is 781964.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153451.3. 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
	LTO1	NM_153451.3	MANE Select	c.157-4A>C		splice_region intron	N/A	NP_703152.1	Q8WV07

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTO1	ENST00000279147.9	TSL:1 MANE Select	c.157-4A>C		splice_region intron	N/A	ENSP00000279147.5	Q8WV07
	LTO1	ENST00000538554.6	TSL:2	c.157-4A>C		splice_region intron	N/A	ENSP00000446428.3	B4DFA5
	LTO1	ENST00000536870.5	TSL:1	c.50+3367A>C		intron	N/A	ENSP00000441984.1	F5GWS9

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

GnomAD2 exomes AF: 0.00660 AC: 1659 AN: 251400 AF XY: 0.00718

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 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

African (AFR) AF: 0.00105 AC: 34 AN: 32330

American (AMR) AF: 0.00439 AC: 196 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 601 AN: 25774

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.0134 AC: 1141 AN: 85038

European-Finnish (FIN) AF: 0.00131 AC: 70 AN: 53336

Middle Eastern (MID) AF: 0.00814 AC: 46 AN: 5654

European-Non Finnish (NFE) AF: 0.00789 AC: 8343 AN: 1057890

Other (OTH) AF: 0.00865 AC: 505 AN: 58414

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

African (AFR) AF: 0.00120 AC: 50 AN: 41522

American (AMR) AF: 0.00347 AC: 53 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00995 AC: 48 AN: 4826

European-Finnish (FIN) AF: 0.000944 AC: 10 AN: 10592

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00747 AC: 508 AN: 68012

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.9
DANN	Benign	0.63
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs142367375; hg19: chr11-69486591;