chr1-64049707-C-T
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_005012.4(ROR1):c.180C>T(p.Leu60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,613,364 control chromosomes in the GnomAD database, including 576,951 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.79 ( 48726 hom., cov: 30)
Exomes 𝑓: 0.85 ( 528225 hom. )
Consequence
ROR1
NM_005012.4 synonymous
NM_005012.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -5.37
Genes affected
ROR1 (HGNC:10256): (receptor tyrosine kinase like orphan receptor 1) This gene encodes a receptor tyrosine kinase-like orphan receptor that modulates neurite growth in the central nervous system. The encoded protein is a glycosylated type I membrane protein that belongs to the ROR subfamily of cell surface receptors. It is a pseudokinase that lacks catalytic activity and may interact with the non-canonical Wnt signalling pathway. This gene is highly expressed during early embryonic development but expressed at very low levels in adult tissues. Increased expression of this gene is associated with B-cell chronic lymphocytic leukaemia. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2012]
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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=-0.77).
BP6
?
Variant 1-64049707-C-T is Benign according to our data. Variant chr1-64049707-C-T is described in ClinVar as [Benign]. Clinvar id is 1240716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-5.37 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ROR1 | NM_005012.4 | c.180C>T | p.Leu60= | synonymous_variant | 3/9 | ENST00000371079.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ROR1 | ENST00000371079.6 | c.180C>T | p.Leu60= | synonymous_variant | 3/9 | 1 | NM_005012.4 | P1 | |
ROR1 | ENST00000371080.5 | c.180C>T | p.Leu60= | synonymous_variant | 3/7 | 1 | |||
ROR1 | ENST00000482426.1 | n.214C>T | non_coding_transcript_exon_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.794 AC: 120668AN: 151882Hom.: 48692 Cov.: 30
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GnomAD3 exomes AF: 0.846 AC: 211561AN: 250144Hom.: 90134 AF XY: 0.845 AC XY: 114321AN XY: 135288
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GnomAD4 exome AF: 0.849 AC: 1240676AN: 1461364Hom.: 528225 Cov.: 52 AF XY: 0.848 AC XY: 616490AN XY: 726968
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GnomAD4 genome ? AF: 0.794 AC: 120757AN: 152000Hom.: 48726 Cov.: 30 AF XY: 0.798 AC XY: 59275AN XY: 74290
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 04, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Hearing loss, autosomal recessive 108 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
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