chr22-46364133-CGTGCGCGAGGAT-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PM4PP3BP6_Very_StrongBS1BS2
The NM_001378328.1(CELSR1):c.8886_8897del(p.Arg2965_Ser2968del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,612,304 control chromosomes in the GnomAD database, including 33 homozygotes. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0080 ( 20 hom., cov: 33)
Exomes 𝑓: 0.00080 ( 13 hom. )
Consequence
CELSR1
NM_001378328.1 inframe_deletion
NM_001378328.1 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.05
Genes affected
CELSR1 (HGNC:1850): (cadherin EGF LAG seven-pass G-type receptor 1) The protein encoded by this gene is a member of the flamingo subfamily, part of the cadherin superfamily. The flamingo subfamily consists of nonclassic-type cadherins; a subpopulation that does not interact with catenins. The flamingo cadherins are located at the plasma membrane and have nine cadherin domains, seven epidermal growth factor-like repeats and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic unique to this subfamily. It is postulated that these proteins are receptors involved in contact-mediated communication, with cadherin domains acting as homophilic binding regions and the EGF-like domains involved in cell adhesion and receptor-ligand interactions. This particular member is a developmentally regulated, neural-specific gene which plays an unspecified role in early embryogenesis. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_001378328.1.
PP3
?
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP6
?
Variant 22-46364133-CGTGCGCGAGGAT-C is Benign according to our data. Variant chr22-46364133-CGTGCGCGAGGAT-C is described in ClinVar as [Benign]. Clinvar id is 716653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00804 (1225/152346) while in subpopulation AFR AF= 0.028 (1162/41574). AF 95% confidence interval is 0.0266. There are 20 homozygotes in gnomad4. There are 585 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1225 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CELSR1 | NM_001378328.1 | c.8886_8897del | p.Arg2965_Ser2968del | inframe_deletion | 34/35 | ENST00000674500.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CELSR1 | ENST00000674500.2 | c.8886_8897del | p.Arg2965_Ser2968del | inframe_deletion | 34/35 | NM_001378328.1 | A2 | ||
CELSR1 | ENST00000262738.9 | c.8886_8897del | p.Arg2965_Ser2968del | inframe_deletion | 34/35 | 1 | P4 | ||
CELSR1 | ENST00000473624.2 | c.639_650del | p.Arg216_Ser219del | inframe_deletion | 5/5 | 1 | |||
CELSR1 | ENST00000674159.1 | n.2329_2340del | non_coding_transcript_exon_variant | 10/11 |
Frequencies
GnomAD3 genomes ? AF: 0.00805 AC: 1225AN: 152228Hom.: 20 Cov.: 33
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GnomAD3 exomes AF: 0.00203 AC: 504AN: 248514Hom.: 7 AF XY: 0.00149 AC XY: 201AN XY: 135070
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GnomAD4 exome AF: 0.000801 AC: 1169AN: 1459958Hom.: 13 AF XY: 0.000625 AC XY: 454AN XY: 726260
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CELSR1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 26, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 30, 2017 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at