rs2247809

Positions:

• chr21-28958129-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LTN1	NM_015565.3	c.2747+257C>T		intron_variant		ENST00000361371.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LTN1	ENST00000361371.10	c.2747+257C>T		intron_variant		1	NM_015565.3	P1
LTN1	ENST00000389194.7	c.2747+257C>T		intron_variant		1		P1
LTN1	ENST00000614971.4	c.2885+257C>T		intron_variant		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

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.537

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.333

Alfa AF: 0.308 Hom.: 1336

Bravo AF: 0.348

Asia WGS AF: 0.371 AC: 1289 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	0.0080
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs2247809; hg19: chr21-30330451;