3-3817248-C-T

Variant names:

• chr3-3817248-C-T
• rs711578
• NM_020873.7:c.-279+17329C>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+17329C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,986 control chromosomes in the GnomAD database, including 20,636 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 0.48 (20636 hom., cov: 33)
• Consequence: LRRN1 NM_020873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7	c.-279+17329C>T		intron_variant	Intron 1 of 1	ENST00000319331.4	NP_065924.3
LRRN1	NM_001324188.2	c.-279+16002C>T		intron_variant	Intron 2 of 2		NP_001311117.1
LRRN1	NM_001324189.2	c.-279+16002C>T		intron_variant	Intron 2 of 2		NP_001311118.1
LRRN1	XM_047448644.1	c.-279+4594C>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.-279+17329C>T		intron_variant	Intron 1 of 1	1	NM_020873.7	ENSP00000314901.3
SUMF1	ENST00000448413.5	n.*342+5486G>A		intron_variant	Intron 11 of 12	2		ENSP00000404384.1
LRRN1	ENST00000496115.1	n.376+16002C>T		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73026 AN: 151868 Hom.: 20642 Cov.: 33

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.676

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.480 AC: 73020 AN: 151986 Hom.: 20636 Cov.: 33 AF XY: 0.479 AC XY: 35609 AN XY: 74302

African (AFR) AF: 0.200 AC: 8275 AN: 41406

American (AMR) AF: 0.457 AC: 6973 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1861 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1108 AN: 5166

South Asian (SAS) AF: 0.365 AC: 1760 AN: 4824

European-Finnish (FIN) AF: 0.727 AC: 7683 AN: 10570

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.641 AC: 43573 AN: 67978

Other (OTH) AF: 0.481 AC: 1014 AN: 2110

Alfa AF: 0.578 Hom.: 110965

Bravo AF: 0.449

Asia WGS AF: 0.274 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.56
PhyloP100		-0.62
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: rs711578; hg19: chr3-3858932;