rs11603541

chr11-69657605-C-Gchr11-69657605-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047427985.1(LOC124902704):c.311G>C(p.Trp104Ser) variant causes a missense 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. 4/4 in silico tools predict 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: LOC124902704 XM_047427985.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.465

Genes affected

LOC124902704 (HGNC:):

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 -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/exons	MANE	UniProt
LOC124902704	XM_047427985.1	c.311G>C	p.Trp104Ser	missense_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTO1	ENST00000538554.6	c.346-953G>C		intron_variant		2
LTO1	ENST00000542515.5	n.826G>C		non_coding_transcript_exon_variant	1/3	2
LTO1	ENST00000569105.5	n.270-953G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12635 AN: 152174 Hom.: 774 Cov.: 33

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

GnomAD3 exomes AF: 0.0657 AC: 8830 AN: 134400 Hom.: 473 AF XY: 0.0653 AC XY: 4778 AN XY: 73142

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 SAS exome AF: 0.0392

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.: 0 AF XY: 0.0767 AC XY: 13276 AN XY: 173132

Gnomad4 AFR exome AF: 0.0484

Gnomad4 AMR exome AF: 0.0211

Gnomad4 ASJ exome AF: 0.0513

Gnomad4 EAS exome AF: 0.00185

Gnomad4 SAS exome AF: 0.0392

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.0830 AC: 12637 AN: 152292 Hom.: 773 Cov.: 33 AF XY: 0.0858 AC XY: 6385 AN XY: 74452

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.00348

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.0597

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
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11603541; hg19: chr11-69472373;