Genetic Variant LRRN1:c.-279+17329C>T (chr3-3817248-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.621

Publications

4 publications found

Variant links:

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]

LRRN1 links:

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

SUMF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRRN1	NM_020873.7	MANE Select	c.-279+17329C>T	intron	N/A	NP_065924.3
LRRN1	NM_001324188.2		c.-279+16002C>T	intron	N/A	NP_001311117.1	Q6UXK5
LRRN1	NM_001324189.2		c.-279+16002C>T	intron	N/A	NP_001311118.1	Q6UXK5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LRRN1	ENST00000319331.4	TSL:1 MANE Select	c.-279+17329C>T	intron	N/A	ENSP00000314901.3	Q6UXK5
LRRN1	ENST00000909966.1		c.-279+16002C>T	intron	N/A	ENSP00000580025.1
LRRN1	ENST00000934601.1		c.-324+17329C>T	intron	N/A	ENSP00000604660.1

Frequencies

GnomAD3 genomes

AF:

0.481

AC:

73026

AN:

151868

Hom.:

20642

Cov.:

show subpopulations

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.:

AF XY:

0.479

AC XY:

35609

AN XY:

74302

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1646

3292

4939

6585

8231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

(source)

DANN

Benign

0.56

PhyloP100

-0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over