Variant rs3749350 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000319331.4(LRRN1):c.396C>A(p.Thr132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,828 control chromosomes in the GnomAD database, including 24,228 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. Synonymous variant affecting the same amino acid position (i.e. T132T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.21 ( 4301 hom., cov: 32)

Exomes 𝑓: 0.15 ( 19927 hom. )

Consequence

LRRN1
ENST00000319331.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.25

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=-3.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRRN1	NM_020873.7 linkuse as main transcript	c.396C>A	p.Thr132=	synonymous_variant	2/2	ENST00000319331.4	NP_065924.3
LRRN1	NM_001324188.2 linkuse as main transcript	c.396C>A	p.Thr132=	synonymous_variant	3/3		NP_001311117.1
LRRN1	NM_001324189.2 linkuse as main transcript	c.396C>A	p.Thr132=	synonymous_variant	3/3		NP_001311118.1
LRRN1	XM_047448644.1 linkuse as main transcript	c.396C>A	p.Thr132=	synonymous_variant	2/2		XP_047304600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRN1	ENST00000319331.4 linkuse as main transcript	c.396C>A	p.Thr132=	synonymous_variant	2/2	1	NM_020873.7	ENSP00000314901	P1
SUMF1	ENST00000448413.5 linkuse as main transcript	c.1192-17528G>T		intron_variant, NMD_transcript_variant		2		ENSP00000404384

Frequencies

GnomAD3 genomes

AF:

0.211

AC:

32004

AN:

151928

Hom.:

4287

Cov.:

show subpopulations

Gnomad AFR

AF:

0.360

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.232

Gnomad ASJ

AF:

0.160

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.0802

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.215

GnomAD3 exomes

AF:

0.188

AC:

47269

AN:

251112

Hom.:

5791

AF XY:

0.181

AC XY:

24612

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.370

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.434

Gnomad SAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.0825

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.150

AC:

219014

AN:

1461782

Hom.:

19927

Cov.:

AF XY:

0.150

AC XY:

109267

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.372

Gnomad4 AMR exome

AF:

0.244

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.221

Gnomad4 FIN exome

AF:

0.0857

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.211

AC:

32063

AN:

152046

Hom.:

4301

Cov.:

AF XY:

0.212

AC XY:

15790

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.232

Gnomad4 ASJ

AF:

0.160

Gnomad4 EAS

AF:

0.413

Gnomad4 SAS

AF:

0.217

Gnomad4 FIN

AF:

0.0802

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.132

Hom.:

1838

Bravo

AF:

0.232

Asia WGS

AF:

0.340

AC:

1183

AN:

3476

EpiCase

AF:

0.125

EpiControl

AF:

0.124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.082

DANN

Benign

0.74

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over