21-28940739-G-T

Variant names:

• chr21-28940739-G-T
• rs2243503
• NM_015565.3:c.4482+481C>A

Variant summary

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

The NM_015565.3(LTN1):​c.4482+481C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,136 control chromosomes in the GnomAD database, including 4,613 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 0.20 (4613 hom., cov: 32)
• Consequence: LTN1 NM_015565.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.663
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTN1	NM_015565.3	c.4482+481C>A		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.4482+481C>A		intron_variant	Intron 25 of 29	1	NM_015565.3	ENSP00000354977.4
LTN1	ENST00000614971.4	c.4620+481C>A		intron_variant	Intron 25 of 29	1		ENSP00000478783.1
LTN1	ENST00000389194.7	c.4482+481C>A		intron_variant	Intron 25 of 29	1		ENSP00000373846.3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30455 AN: 152018 Hom.: 4614 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0999

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0486

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.200 AC: 30494 AN: 152136 Hom.: 4613 Cov.: 32 AF XY: 0.196 AC XY: 14582 AN XY: 74386

African (AFR) AF: 0.409 AC: 16935 AN: 41442

American (AMR) AF: 0.195 AC: 2985 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0999 AC: 347 AN: 3472

East Asian (EAS) AF: 0.371 AC: 1917 AN: 5172

South Asian (SAS) AF: 0.125 AC: 606 AN: 4830

European-Finnish (FIN) AF: 0.0486 AC: 516 AN: 10614

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0989 AC: 6723 AN: 68010

Other (OTH) AF: 0.178 AC: 376 AN: 2108

Alfa AF: 0.123 Hom.: 2763

Bravo AF: 0.223

Asia WGS AF: 0.245 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.37
PhyloP100		-0.66
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: rs2243503; hg19: chr21-30313061;