rs12054065

Variant names:

• chr3-3809563-A-C
• rs12054065
• NM_020873.7:c.-279+9644A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-3809563-A-C
• chr3-3809563-A-G
• chr3-3809563-A-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+9644A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,180 control chromosomes in the GnomAD database, including 4,620 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 0.21 (4620 hom., cov: 33)
• Consequence: LRRN1 NM_020873.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 1 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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.392 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020873.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRN1	NM_020873.7	MANE Select	c.-279+9644A>C		intron	N/A	NP_065924.3
	LRRN1	NM_001324188.2		c.-279+8317A>C		intron	N/A	NP_001311117.1	Q6UXK5
	LRRN1	NM_001324189.2		c.-279+8317A>C		intron	N/A	NP_001311118.1	Q6UXK5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRN1	ENST00000319331.4	TSL:1 MANE Select	c.-279+9644A>C		intron	N/A	ENSP00000314901.3	Q6UXK5
	LRRN1	ENST00000909966.1		c.-279+8317A>C		intron	N/A	ENSP00000580025.1
	LRRN1	ENST00000934601.1		c.-324+9644A>C		intron	N/A	ENSP00000604660.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31784 AN: 152062 Hom.: 4607 Cov.: 33

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.0731

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.209 AC: 31834 AN: 152180 Hom.: 4620 Cov.: 33 AF XY: 0.213 AC XY: 15822 AN XY: 74414

African (AFR) AF: 0.397 AC: 16464 AN: 41454

American (AMR) AF: 0.171 AC: 2611 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 589 AN: 3472

East Asian (EAS) AF: 0.255 AC: 1322 AN: 5182

South Asian (SAS) AF: 0.377 AC: 1818 AN: 4826

European-Finnish (FIN) AF: 0.0731 AC: 776 AN: 10620

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7732 AN: 68006

Other (OTH) AF: 0.187 AC: 395 AN: 2108

Alfa AF: 0.140 Hom.: 3452

Bravo AF: 0.223

Asia WGS AF: 0.325 AC: 1129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.77
PhyloP100		0.26
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: rs12054065; hg19: chr3-3851247;