Genetic Variant LRRN1:c.-279+21676T>C (chr3-3821595-T-C) – 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+21676T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,094 control chromosomes in the GnomAD database, including 34,170 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 0.65 ( 34170 hom., cov: 32)

Consequence

LRRN1
NM_020873.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.491

Publications

6 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, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, ClinGen, 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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LRRN1	NM_020873.7 link	c.-279+21676T>C	intron_variant	Intron 1 of 1	ENST00000319331.4	NP_065924.3	Q6UXK5A8K6Q2
LRRN1	NM_001324188.2 link	c.-279+20349T>C	intron_variant	Intron 2 of 2		NP_001311117.1	Q6UXK5
LRRN1	NM_001324189.2 link	c.-279+20349T>C	intron_variant	Intron 2 of 2		NP_001311118.1	Q6UXK5
LRRN1	XM_047448644.1 link	c.-279+8941T>C	intron_variant	Intron 1 of 1		XP_047304600.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LRRN1	ENST00000319331.4 link	c.-279+21676T>C	intron_variant	Intron 1 of 1	1	NM_020873.7	ENSP00000314901.3	Q6UXK5
SUMF1	ENST00000448413.5 link	n.*342+1139A>G	intron_variant	Intron 11 of 12	2		ENSP00000404384.1	F5GXA0
LRRN1	ENST00000496115.1 link	n.376+20349T>C	intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99095

AN:

151976

Hom.:

34168

Cov.:

show subpopulations

Gnomad AFR

AF:

0.412

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.644

Gnomad ASJ

AF:

0.770

Gnomad EAS

AF:

0.517

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.826

Gnomad MID

AF:

0.801

Gnomad NFE

AF:

0.773

Gnomad OTH

AF:

0.670

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

GnomAD4 genome

AF:

0.652

AC:

99132

AN:

152094

Hom.:

34170

Cov.:

AF XY:

0.654

AC XY:

48618

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.411

AC:

17051

AN:

41464

American (AMR)

AF:

0.644

AC:

9847

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.770

AC:

2674

AN:

3472

East Asian (EAS)

AF:

0.518

AC:

2674

AN:

5164

South Asian (SAS)

AF:

0.674

AC:

3252

AN:

4822

European-Finnish (FIN)

AF:

0.826

AC:

8758

AN:

10598

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.773

AC:

52571

AN:

67970

Other (OTH)

AF:

0.668

AC:

1413

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1587

3173

4760

6346

7933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.730

Hom.:

20068

Bravo

AF:

0.625

Asia WGS

AF:

0.550

AC:

1910

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.2

(source)

DANN

Benign

0.69

PhyloP100

0.49

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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3-3821595-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over