rs13100776

Variant names:

• chr3-3842373-G-T
• rs13100776
• NM_020873.7:c.-278-1991G>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.-278-1991G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,338 control chromosomes in the GnomAD database, including 1,277 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 0.13 (1277 hom., cov: 31)
• Consequence: LRRN1 NM_020873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.390
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7	c.-278-1991G>T		intron_variant	Intron 1 of 1	ENST00000319331.4	NP_065924.3
LRRN1	NM_001324188.2	c.-278-1991G>T		intron_variant	Intron 2 of 2		NP_001311117.1
LRRN1	NM_001324189.2	c.-278-1991G>T		intron_variant	Intron 2 of 2		NP_001311118.1
LRRN1	XM_047448644.1	c.-278-1991G>T		intron_variant	Intron 1 of 1		XP_047304600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRN1	ENST00000319331.4	c.-278-1991G>T		intron_variant	Intron 1 of 1	1	NM_020873.7	ENSP00000314901.3
SUMF1	ENST00000448413.5	n.1192-14864C>A		intron_variant	Intron 9 of 12	2		ENSP00000404384.1
LRRN1	ENST00000496115.1	n.377-1991G>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19577 AN: 151220 Hom.: 1278 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.0658

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.129 AC: 19583 AN: 151338 Hom.: 1277 Cov.: 31 AF XY: 0.130 AC XY: 9632 AN XY: 73868

African (AFR) AF: 0.148 AC: 6078 AN: 41190

American (AMR) AF: 0.158 AC: 2398 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3470

East Asian (EAS) AF: 0.157 AC: 805 AN: 5136

South Asian (SAS) AF: 0.167 AC: 796 AN: 4766

European-Finnish (FIN) AF: 0.0658 AC: 687 AN: 10434

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7975 AN: 67874

Other (OTH) AF: 0.136 AC: 287 AN: 2110

Alfa AF: 0.124 Hom.: 1058

Bravo AF: 0.135

Asia WGS AF: 0.172 AC: 601 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.045
DANN	Benign	0.52
PhyloP100		-0.39
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: rs13100776; hg19: chr3-3884057;