rs2243552

Positions:

• chr21-28946144-T-G

Variant summary

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

The NM_015565.3(LTN1):​c.3623+8A>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 0.239 in 1,565,384 control chromosomes in the GnomAD database, including 53,867 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8540 hom., cov: 32)
  • Exomes 𝑓: 0.23 (45327 hom.)
• Consequence: LTN1 NM_015565.3 splice_region, intron
• Scores: Splicing: ADA: 0.00001729
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

Genes affected

LTN1 (HGNC:13082): (listerin E3 ubiquitin protein ligase 1) Like most RING finger proteins, LTN1 functions as an E3 ubiquitin ligase (Chu et al., 2009 [PubMed 19196968]).[supplied by OMIM, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTN1	NM_015565.3	c.3623+8A>C		splice_region_variant, intron_variant		ENST00000361371.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTN1	ENST00000361371.10	c.3623+8A>C		splice_region_variant, intron_variant		1	NM_015565.3	P1
LTN1	ENST00000389194.7	c.3623+8A>C		splice_region_variant, intron_variant		1		P1
LTN1	ENST00000614971.4	c.3761+8A>C		splice_region_variant, intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46491 AN: 151814 Hom.: 8544 Cov.: 32

Gnomad AFR AF: 0.449

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.301

GnomAD3 exomes AF: 0.283 AC: 63818 AN: 225456 Hom.: 12070 AF XY: 0.265 AC XY: 32347 AN XY: 122164

Gnomad AFR exome AF: 0.452

Gnomad AMR exome AF: 0.469

Gnomad ASJ exome AF: 0.213

Gnomad EAS exome AF: 0.705

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.215

Gnomad OTH exome AF: 0.246

GnomAD4 exome AF: 0.231 AC: 327096 AN: 1413450 Hom.: 45327 Cov.: 27 AF XY: 0.228 AC XY: 160204 AN XY: 703990

Gnomad4 AFR exome AF: 0.461

Gnomad4 AMR exome AF: 0.455

Gnomad4 ASJ exome AF: 0.215

Gnomad4 EAS exome AF: 0.691

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.135

Gnomad4 NFE exome AF: 0.210

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.306 AC: 46527 AN: 151934 Hom.: 8540 Cov.: 32 AF XY: 0.303 AC XY: 22523 AN XY: 74280

Gnomad4 AFR AF: 0.448

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.215

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.302

Alfa AF: 0.236 Hom.: 10282

Bravo AF: 0.338

Asia WGS AF: 0.421 AC: 1458 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2243552; hg19: chr21-30318466;