rs2247809

Variant names:

• chr21-28958129-G-A
• rs2247809
• NM_015565.3:c.2747+257C>T

Variant summary

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

The NM_015565.3(LTN1):​c.2747+257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,030 control chromosomes in the GnomAD database, including 8,728 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 0.32 (8728 hom., cov: 32)
• Consequence: LTN1 NM_015565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 10 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 (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015565.3. 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
	LTN1	NM_015565.3	MANE Select	c.2747+257C>T		intron	N/A	NP_056380.3	O94822-1
	LTN1	NM_001320766.2		c.2705+257C>T		intron	N/A	NP_001307695.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTN1	ENST00000361371.10	TSL:1 MANE Select	c.2747+257C>T		intron	N/A	ENSP00000354977.4	O94822-1
	LTN1	ENST00000614971.4	TSL:1	c.2885+257C>T		intron	N/A	ENSP00000478783.1	O94822-3
	LTN1	ENST00000389194.7	TSL:1	c.2747+257C>T		intron	N/A	ENSP00000373846.3	O94822-1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49298 AN: 151912 Hom.: 8733 Cov.: 32

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.324 AC: 49327 AN: 152030 Hom.: 8728 Cov.: 32 AF XY: 0.321 AC XY: 23826 AN XY: 74316

African (AFR) AF: 0.426 AC: 17623 AN: 41412

American (AMR) AF: 0.388 AC: 5927 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1009 AN: 3466

East Asian (EAS) AF: 0.537 AC: 2779 AN: 5172

South Asian (SAS) AF: 0.221 AC: 1064 AN: 4818

European-Finnish (FIN) AF: 0.186 AC: 1971 AN: 10578

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17950 AN: 67982

Other (OTH) AF: 0.333 AC: 703 AN: 2108

Alfa AF: 0.312 Hom.: 1411

Bravo AF: 0.348

Asia WGS AF: 0.371 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.0080
DANN	Benign	0.36
PhyloP100		-2.6
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: rs2247809; hg19: chr21-30330451;