chr3-3845037-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020873.7(LRRN1):​c.396C>T​(p.Thr132=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000957 in 1,613,926 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 9 hom., cov: 32)
Exomes 𝑓: 0.00051 ( 4 hom. )

Consequence

LRRN1
NM_020873.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]
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 -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 3-3845037-C-T is Benign according to our data. Variant chr3-3845037-C-T is described in ClinVar as [Benign]. Clinvar id is 716843.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.24 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00529 (805/152080) while in subpopulation AFR AF= 0.0188 (779/41450). AF 95% confidence interval is 0.0177. There are 9 homozygotes in gnomad4. There are 366 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 805 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRRN1NM_020873.7 linkuse as main transcriptc.396C>T p.Thr132= synonymous_variant 2/2 ENST00000319331.4 NP_065924.3
LRRN1NM_001324188.2 linkuse as main transcriptc.396C>T p.Thr132= synonymous_variant 3/3 NP_001311117.1
LRRN1NM_001324189.2 linkuse as main transcriptc.396C>T p.Thr132= synonymous_variant 3/3 NP_001311118.1
LRRN1XM_047448644.1 linkuse as main transcriptc.396C>T p.Thr132= 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.396C>T p.Thr132= synonymous_variant 2/21 NM_020873.7 ENSP00000314901 P1
SUMF1ENST00000448413.5 linkuse as main transcriptc.1192-17528G>A intron_variant, NMD_transcript_variant 2 ENSP00000404384

Frequencies

GnomAD3 genomes
AF:
0.00530
AC:
806
AN:
151962
Hom.:
9
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0189
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000852
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00148
AC:
372
AN:
251112
Hom.:
2
AF XY:
0.00106
AC XY:
144
AN XY:
135726
show subpopulations
Gnomad AFR exome
AF:
0.0211
Gnomad AMR exome
AF:
0.000665
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000440
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000506
AC:
740
AN:
1461846
Hom.:
4
Cov.:
75
AF XY:
0.000437
AC XY:
318
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0188
Gnomad4 AMR exome
AF:
0.000850
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.000695
GnomAD4 genome
AF:
0.00529
AC:
805
AN:
152080
Hom.:
9
Cov.:
32
AF XY:
0.00492
AC XY:
366
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0188
Gnomad4 AMR
AF:
0.000850
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.0000270
Hom.:
1838
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.50
DANN
Benign
0.85

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: rs3749350; hg19: chr3-3886721; API