rs3749350

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020873.7(LRRN1):​c.396C>A​(p.Thr132Thr) 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
NM_020873.7 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.25

Publications

14 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]
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank MANE Protein UniProt
LRRN1NM_020873.7 linkc.396C>A p.Thr132Thr synonymous_variant Exon 2 of 2 ENST00000319331.4 NP_065924.3 Q6UXK5A8K6Q2
LRRN1NM_001324188.2 linkc.396C>A p.Thr132Thr synonymous_variant Exon 3 of 3 NP_001311117.1 Q6UXK5
LRRN1NM_001324189.2 linkc.396C>A p.Thr132Thr synonymous_variant Exon 3 of 3 NP_001311118.1 Q6UXK5
LRRN1XM_047448644.1 linkc.396C>A p.Thr132Thr synonymous_variant Exon 2 of 2 XP_047304600.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRN1ENST00000319331.4 linkc.396C>A p.Thr132Thr synonymous_variant Exon 2 of 2 1 NM_020873.7 ENSP00000314901.3 Q6UXK5
SUMF1ENST00000448413.5 linkn.1192-17528G>T intron_variant Intron 9 of 12 2 ENSP00000404384.1 F5GXA0

Frequencies

GnomAD3 genomes
AF:
0.211
AC:
32004
AN:
151928
Hom.:
4287
Cov.:
32
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
GnomAD2 exomes
AF:
0.188
AC:
47269
AN:
251112
AF XY:
0.181
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 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.:
75
AF XY:
0.150
AC XY:
109267
AN XY:
727212
show subpopulations
African (AFR)
AF:
0.372
AC:
12448
AN:
33476
American (AMR)
AF:
0.244
AC:
10916
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
0.171
AC:
4458
AN:
26136
East Asian (EAS)
AF:
0.413
AC:
16378
AN:
39676
South Asian (SAS)
AF:
0.221
AC:
19065
AN:
86252
European-Finnish (FIN)
AF:
0.0857
AC:
4577
AN:
53418
Middle Eastern (MID)
AF:
0.177
AC:
1023
AN:
5766
European-Non Finnish (NFE)
AF:
0.125
AC:
139498
AN:
1111944
Other (OTH)
AF:
0.176
AC:
10651
AN:
60392
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.476
Heterozygous variant carriers
0
11091
22183
33274
44366
55457
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
5516
11032
16548
22064
27580
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.211
AC:
32063
AN:
152046
Hom.:
4301
Cov.:
32
AF XY:
0.212
AC XY:
15790
AN XY:
74336
show subpopulations
African (AFR)
AF:
0.360
AC:
14924
AN:
41430
American (AMR)
AF:
0.232
AC:
3545
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.160
AC:
554
AN:
3472
East Asian (EAS)
AF:
0.413
AC:
2133
AN:
5160
South Asian (SAS)
AF:
0.217
AC:
1044
AN:
4814
European-Finnish (FIN)
AF:
0.0802
AC:
848
AN:
10578
Middle Eastern (MID)
AF:
0.106
AC:
31
AN:
292
European-Non Finnish (NFE)
AF:
0.124
AC:
8459
AN:
67992
Other (OTH)
AF:
0.223
AC:
470
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.507
Heterozygous variant carriers
0
1231
2463
3694
4926
6157
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
326
652
978
1304
1630
<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:
0.147
Hom.:
3440
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
PhyloP100
-3.2
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3749350; hg19: chr3-3886721; COSMIC: COSV60012751; COSMIC: COSV60012751; API