Variant 3-3845100-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_020873.7(LRRN1):c.459C>T(p.Asn153=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00798 in 1,614,056 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0082 ( 66 hom. )

Consequence

LRRN1
NM_020873.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.98

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 3-3845100-C-T is Benign according to our data. Variant chr3-3845100-C-T is described in ClinVar as [Benign]. Clinvar id is 778063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.98 with no splicing effect.

BS2

High AC in GnomAd4 at 871 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
LRRN1	NM_020873.7 linkuse as main transcript	c.459C>T	p.Asn153=	synonymous_variant	2/2	ENST00000319331.4
LRRN1	NM_001324188.2 linkuse as main transcript	c.459C>T	p.Asn153=	synonymous_variant	3/3
LRRN1	NM_001324189.2 linkuse as main transcript	c.459C>T	p.Asn153=	synonymous_variant	3/3
LRRN1	XM_047448644.1 linkuse as main transcript	c.459C>T	p.Asn153=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRN1	ENST00000319331.4 linkuse as main transcript	c.459C>T	p.Asn153=	synonymous_variant	2/2	1	NM_020873.7	P1
SUMF1	ENST00000448413.5 linkuse as main transcript	c.1192-17591G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00574

AC:

873

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00570

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00976

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00501

AC:

1257

AN:

251008

Hom.:

AF XY:

0.00503

AC XY:

682

AN XY:

135634

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00157

Gnomad FIN exome

AF:

0.00125

Gnomad NFE exome

AF:

0.00866

Gnomad OTH exome

AF:

0.00588

GnomAD4 exome

AF:

0.00821

AC:

12002

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

5831

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.00218

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00173

Gnomad4 FIN exome

AF:

0.00137

Gnomad4 NFE exome

AF:

0.00997

Gnomad4 OTH exome

AF:

0.00639

GnomAD4 genome

AF:

0.00572

AC:

871

AN:

152224

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

371

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.00569

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00973

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.00805

Hom.:

Bravo

AF:

0.00634

Asia WGS

AF:

0.000867

AC:

AN:

3476

EpiCase

AF:

0.00802

EpiControl

AF:

0.00800

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.1

DANN

Benign

0.81

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