chr3-3845100-C-T

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

2

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]
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 -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 Protein UniProt
LRRN1NM_020873.7 linkuse as main transcriptc.459C>T p.Asn153= synonymous_variant 2/2 ENST00000319331.4 NP_065924.3
LRRN1NM_001324188.2 linkuse as main transcriptc.459C>T p.Asn153= synonymous_variant 3/3 NP_001311117.1
LRRN1NM_001324189.2 linkuse as main transcriptc.459C>T p.Asn153= synonymous_variant 3/3 NP_001311118.1
LRRN1XM_047448644.1 linkuse as main transcriptc.459C>T p.Asn153= synonymous_variant 2/2 XP_047304600.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRRN1ENST00000319331.4 linkuse as main transcriptc.459C>T p.Asn153= synonymous_variant 2/21 NM_020873.7 ENSP00000314901 P1
SUMF1ENST00000448413.5 linkuse as main transcriptc.1192-17591G>A intron_variant, NMD_transcript_variant 2 ENSP00000404384

Frequencies

GnomAD3 genomes
AF:
0.00574
AC:
873
AN:
152106
Hom.:
6
Cov.:
32
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.:
4
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.:
66
Cov.:
75
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.:
6
Cov.:
32
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.:
2
Bravo
AF:
0.00634
Asia WGS
AF:
0.000867
AC:
3
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 submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Benign, criteria provided, single submitternot providedBreakthrough 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.

Other links and lift over

dbSNP: rs113168029; hg19: chr3-3886784; COSMIC: COSV100076361; COSMIC: COSV100076361; API