chr3-3845625-C-T
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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
NM_020873.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.736
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
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
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
Synonymous conserved (PhyloP=-0.736 with no splicing effect.
BS2
High AC in GnomAd4 at 680 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LRRN1 | NM_020873.7 | c.984C>T | p.Ile328= | synonymous_variant | 2/2 | ENST00000319331.4 | |
LRRN1 | NM_001324188.2 | c.984C>T | p.Ile328= | synonymous_variant | 3/3 | ||
LRRN1 | NM_001324189.2 | c.984C>T | p.Ile328= | synonymous_variant | 3/3 | ||
LRRN1 | XM_047448644.1 | c.984C>T | p.Ile328= | synonymous_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LRRN1 | ENST00000319331.4 | c.984C>T | p.Ile328= | synonymous_variant | 2/2 | 1 | NM_020873.7 | P1 | |
SUMF1 | ENST00000448413.5 | c.1192-18116G>A | intron_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00448 AC: 681AN: 152058Hom.: 3 Cov.: 32
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GnomAD3 exomes AF: 0.00557 AC: 1398AN: 251080Hom.: 18 AF XY: 0.00523 AC XY: 710AN XY: 135686
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GnomAD4 exome AF: 0.00488 AC: 7131AN: 1461866Hom.: 41 Cov.: 74 AF XY: 0.00470 AC XY: 3415AN XY: 727240
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GnomAD4 genome AF: 0.00447 AC: 680AN: 152174Hom.: 3 Cov.: 32 AF XY: 0.00495 AC XY: 368AN XY: 74382
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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 submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2023 | LRRN1: BP4, BP7, BS2 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at