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GeneBe

3-3845625-C-T

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

2

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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.736 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 681 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LRRN1NM_020873.7 linkuse as main transcriptc.984C>T p.Ile328= synonymous_variant 2/2 ENST00000319331.4
LRRN1NM_001324188.2 linkuse as main transcriptc.984C>T p.Ile328= synonymous_variant 3/3
LRRN1NM_001324189.2 linkuse as main transcriptc.984C>T p.Ile328= synonymous_variant 3/3
LRRN1XM_047448644.1 linkuse as main transcriptc.984C>T p.Ile328= synonymous_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LRRN1ENST00000319331.4 linkuse as main transcriptc.984C>T p.Ile328= synonymous_variant 2/21 NM_020873.7 P1
SUMF1ENST00000448413.5 linkuse as main transcriptc.1192-18116G>A intron_variant, NMD_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00448
AC:
681
AN:
152058
Hom.:
3
Cov.:
32
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.:
18
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.:
41
Cov.:
74
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00447
AC:
680
AN:
152174
Hom.:
3
Cov.:
32
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.:
0
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023LRRN1: 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.

Other links and lift over

dbSNP: rs142045330; hg19: chr3-3887309; API