Variant 3-3845625-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020873.7(LRRN1):c.984C>T(p.Ile328=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,614,040 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 41 hom. )

Consequence

LRRN1
NM_020873.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.736

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 3-3845625-C-T is Benign according to our data. Variant chr3-3845625-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653446.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.736 with no splicing effect.

BS2

High AC in GnomAd4 at 680 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRRN1	NM_020873.7 linkuse as main transcript	c.984C>T	p.Ile328=	synonymous_variant	2/2	ENST00000319331.4
LRRN1	NM_001324188.2 linkuse as main transcript	c.984C>T	p.Ile328=	synonymous_variant	3/3
LRRN1	NM_001324189.2 linkuse as main transcript	c.984C>T	p.Ile328=	synonymous_variant	3/3
LRRN1	XM_047448644.1 linkuse as main transcript	c.984C>T	p.Ile328=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRN1	ENST00000319331.4 linkuse as main transcript	c.984C>T	p.Ile328=	synonymous_variant	2/2	1	NM_020873.7	P1
SUMF1	ENST00000448413.5 linkuse as main transcript	c.1192-18116G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00448

AC:

681

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0247

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00456

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00557

AC:

1398

AN:

251080

Hom.:

AF XY:

0.00523

AC XY:

710

AN XY:

135686

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0256

Gnomad NFE exome

AF:

0.00619

Gnomad OTH exome

AF:

0.00670

GnomAD4 exome

AF:

0.00488

AC:

7131

AN:

1461866

Hom.:

Cov.:

AF XY:

0.00470

AC XY:

3415

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000597

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.00176

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0253

Gnomad4 NFE exome

AF:

0.00481

Gnomad4 OTH exome

AF:

0.00462

GnomAD4 genome

AF:

0.00447

AC:

680

AN:

152174

Hom.:

Cov.:

AF XY:

0.00495

AC XY:

368

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0247

Gnomad4 NFE

AF:

0.00456

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00281

EpiCase

AF:

0.00376

EpiControl

AF:

0.00450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

LRRN1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

6.7

DANN

Benign

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over