21-28937230-T-C

Variant names:

• chr21-28937230-T-C
• rs2832141
• NM_015565.3:c.4483-533A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015565.3(LTN1):​c.4483-533A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,084 control chromosomes in the GnomAD database, including 7,702 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7702 hom., cov: 32)
• Consequence: LTN1 NM_015565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.339 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTN1	NM_015565.3	c.4483-533A>G		intron_variant	Intron 25 of 29	ENST00000361371.10	NP_056380.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTN1	ENST00000361371.10	c.4483-533A>G		intron_variant	Intron 25 of 29	1	NM_015565.3	ENSP00000354977.4
LTN1	ENST00000614971.4	c.4621-533A>G		intron_variant	Intron 25 of 29	1		ENSP00000478783.1
LTN1	ENST00000389194.7	c.4483-533A>G		intron_variant	Intron 25 of 29	1		ENSP00000373846.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47612 AN: 151966 Hom.: 7694 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.333

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47657 AN: 152084 Hom.: 7702 Cov.: 32 AF XY: 0.314 AC XY: 23336 AN XY: 74350

African (AFR) AF: 0.286 AC: 11850 AN: 41488

American (AMR) AF: 0.260 AC: 3981 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3470

East Asian (EAS) AF: 0.130 AC: 675 AN: 5178

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4820

European-Finnish (FIN) AF: 0.374 AC: 3949 AN: 10570

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23285 AN: 67950

Other (OTH) AF: 0.330 AC: 697 AN: 2114

Alfa AF: 0.328 Hom.: 31167

Bravo AF: 0.299

Asia WGS AF: 0.264 AC: 918 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.021
DANN	Benign	0.32
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs2832141; hg19: chr21-30309552;