21-28937264-T-C

Variant names:

• chr21-28937264-T-C
• rs2246777
• NM_015565.3:c.4483-567A>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.4483-567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 152,090 control chromosomes in the GnomAD database, including 30,084 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 0.62 (30084 hom., cov: 33)
• Consequence: LTN1 NM_015565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTN1	NM_015565.3	c.4483-567A>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.4483-567A>G		intron_variant	Intron 25 of 29	1	NM_015565.3	ENSP00000354977.4
LTN1	ENST00000614971.4	c.4621-567A>G		intron_variant	Intron 25 of 29	1		ENSP00000478783.1
LTN1	ENST00000389194.7	c.4483-567A>G		intron_variant	Intron 25 of 29	1		ENSP00000373846.3

Frequencies

GnomAD3 genomes AF: 0.619 AC: 94024 AN: 151972 Hom.: 30049 Cov.: 33

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.490

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.619 AC: 94115 AN: 152090 Hom.: 30084 Cov.: 33 AF XY: 0.616 AC XY: 45797 AN XY: 74356

African (AFR) AF: 0.779 AC: 32326 AN: 41486

American (AMR) AF: 0.630 AC: 9630 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3468

East Asian (EAS) AF: 0.821 AC: 4261 AN: 5188

South Asian (SAS) AF: 0.530 AC: 2555 AN: 4818

European-Finnish (FIN) AF: 0.490 AC: 5187 AN: 10576

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.535 AC: 36366 AN: 67956

Other (OTH) AF: 0.623 AC: 1314 AN: 2110

Alfa AF: 0.582 Hom.: 10192

Bravo AF: 0.638

Asia WGS AF: 0.686 AC: 2388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.0070
DANN	Benign	0.48
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: rs2246777; hg19: chr21-30309586;