rs772619184
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6BP7BS1
The NM_001040616.3(LINS1):c.1632C>T(p.Asn544=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000446 in 1,613,456 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000049 ( 1 hom. )
Consequence
LINS1
NM_001040616.3 synonymous
NM_001040616.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.857
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 -8 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant 15-100569880-G-A is Benign according to our data. Variant chr15-100569880-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211381.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
BP7
?
Synonymous conserved (PhyloP=0.857 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000486 (71/1461262) while in subpopulation SAS AF= 0.000731 (63/86126). AF 95% confidence interval is 0.000587. There are 1 homozygotes in gnomad4_exome. There are 49 alleles in male gnomad4_exome subpopulation. Median coverage is 34. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LINS1 | NM_001040616.3 | c.1632C>T | p.Asn544= | synonymous_variant | 7/7 | ENST00000314742.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LINS1 | ENST00000314742.13 | c.1632C>T | p.Asn544= | synonymous_variant | 7/7 | 5 | NM_001040616.3 | P1 | |
LINS1 | ENST00000559169.1 | n.1907C>T | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
LINS1 | ENST00000560783.1 | c.191+3771C>T | intron_variant, NMD_transcript_variant | 5 | |||||
LINS1 | ENST00000561233.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000108 AC: 27AN: 250966Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135618
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GnomAD4 exome AF: 0.0000486 AC: 71AN: 1461262Hom.: 1 Cov.: 34 AF XY: 0.0000674 AC XY: 49AN XY: 726806
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 10, 2014 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | LINS1: BP4, BP7 - |
Computational scores
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Name
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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