rs1488454

Variant names:

• chr3-3805121-C-T
• rs1488454
• NM_020873.7:c.-279+5202C>T

Variant summary

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

The NM_020873.7(LRRN1):​c.-279+5202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,172 control chromosomes in the GnomAD database, including 53,711 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 0.84 (53711 hom., cov: 32)
• Consequence: LRRN1 NM_020873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 5 publications found

Genes affected

LRRN1 (HGNC:20980): (leucine rich repeat neuronal 1) Predicted to act upstream of or within positive regulation of synapse assembly. Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

SUMF1 (HGNC:20376): (sulfatase modifying factor 1) This gene encodes an enzyme that catalyzes the hydrolysis of sulfate esters by oxidizing a cysteine residue in the substrate sulfatase to an active site 3-oxoalanine residue, which is also known as C-alpha-formylglycine. Mutations in this gene cause multiple sulfatase deficiency, a lysosomal storage disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2009]

SUMF1 Gene-Disease associations (from GenCC):

• mucosulfatidosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, G2P

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 (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7	c.-279+5202C>T		intron_variant	Intron 1 of 1	ENST00000319331.4	NP_065924.3
LRRN1	NM_001324188.2	c.-279+3875C>T		intron_variant	Intron 2 of 2		NP_001311117.1
LRRN1	NM_001324189.2	c.-279+3875C>T		intron_variant	Intron 2 of 2		NP_001311118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRN1	ENST00000319331.4	c.-279+5202C>T		intron_variant	Intron 1 of 1	1	NM_020873.7	ENSP00000314901.3
SUMF1	ENST00000448413.5	n.*343-16047G>A		intron_variant	Intron 11 of 12	2		ENSP00000404384.1
LRRN1	ENST00000496115.1	n.376+3875C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127669 AN: 152054 Hom.: 53676 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.801

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.843

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.836

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.840 AC: 127762 AN: 152172 Hom.: 53711 Cov.: 32 AF XY: 0.841 AC XY: 62570 AN XY: 74398

African (AFR) AF: 0.858 AC: 35604 AN: 41504

American (AMR) AF: 0.821 AC: 12553 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.801 AC: 2781 AN: 3472

East Asian (EAS) AF: 0.799 AC: 4127 AN: 5164

South Asian (SAS) AF: 0.844 AC: 4068 AN: 4822

European-Finnish (FIN) AF: 0.852 AC: 9029 AN: 10592

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.836 AC: 56833 AN: 68010

Other (OTH) AF: 0.832 AC: 1759 AN: 2114

Alfa AF: 0.835 Hom.: 89360

Bravo AF: 0.838

Asia WGS AF: 0.814 AC: 2831 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	0.35
DANN	Benign	0.36
PhyloP100		-0.50
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: rs1488454; hg19: chr3-3846805;