rs144513217
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001040616.3(LINS1):āc.1479T>Cā(p.Cys493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000328 in 1,557,222 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00039 ( 0 hom., cov: 32)
Exomes š: 0.00032 ( 3 hom. )
Consequence
LINS1
NM_001040616.3 synonymous
NM_001040616.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0820
Genes affected
LINS1 (HGNC:30922): (lines homolog 1) The Drosophila segment polarity gene lin encodes a protein, lines, which plays important roles in development of the epidermis and hindgut. This gene encodes a protein containing a lines-like domain. This gene is located on chromosome 15 and clustered with the gene encoding ankyrin repeat and SOCS box-containing protein 7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2017]
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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=-0.56).
BP6
Variant 15-100570033-A-G is Benign according to our data. Variant chr15-100570033-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 435759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.082 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000387 (59/152362) while in subpopulation AMR AF= 0.000914 (14/15310). AF 95% confidence interval is 0.000552. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LINS1 | NM_001040616.3 | c.1479T>C | p.Cys493= | synonymous_variant | 7/7 | ENST00000314742.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LINS1 | ENST00000314742.13 | c.1479T>C | p.Cys493= | synonymous_variant | 7/7 | 5 | NM_001040616.3 | P1 | |
LINS1 | ENST00000559169.1 | n.1754T>C | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
LINS1 | ENST00000561233.1 | n.356T>C | non_coding_transcript_exon_variant | 2/2 | 3 | ||||
LINS1 | ENST00000560783.1 | c.191+3618T>C | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000388 AC: 59AN: 152244Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000358 AC: 74AN: 206480Hom.: 0 AF XY: 0.000420 AC XY: 47AN XY: 111848
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GnomAD4 exome AF: 0.000321 AC: 451AN: 1404860Hom.: 3 Cov.: 31 AF XY: 0.000329 AC XY: 229AN XY: 695744
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GnomAD4 genome AF: 0.000387 AC: 59AN: 152362Hom.: 0 Cov.: 32 AF XY: 0.000362 AC XY: 27AN XY: 74512
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | LINS1: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 09, 2016 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 20, 2017 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at