22-46364052-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_001378328.1(CELSR1):c.8979C>T(p.Asn2993Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 1,612,120 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 Likely benign (no stars).
Frequency
Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0030 ( 13 hom. )
Consequence
CELSR1
NM_001378328.1 synonymous
NM_001378328.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.86
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 -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 22-46364052-G-A is Benign according to our data. Variant chr22-46364052-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3046159.Status of the report is no_assertion_criteria_provided, 0 stars.
BP7
Synonymous conserved (PhyloP=-1.86 with no splicing effect.
BS2
High AC in GnomAd4 at 342 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CELSR1 | NM_001378328.1 | c.8979C>T | p.Asn2993Asn | synonymous_variant | 34/35 | ENST00000674500.2 | NP_001365257.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CELSR1 | ENST00000674500.2 | c.8979C>T | p.Asn2993Asn | synonymous_variant | 34/35 | NM_001378328.1 | ENSP00000501367.2 | |||
CELSR1 | ENST00000262738.9 | c.8979C>T | p.Asn2993Asn | synonymous_variant | 34/35 | 1 | ENSP00000262738.3 | |||
CELSR1 | ENST00000473624.2 | c.732C>T | p.Asn244Asn | synonymous_variant | 5/5 | 1 | ENSP00000501353.1 | |||
CELSR1 | ENST00000674159.1 | n.2422C>T | non_coding_transcript_exon_variant | 10/11 |
Frequencies
GnomAD3 genomes AF: 0.00225 AC: 342AN: 152224Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00258 AC: 635AN: 245832Hom.: 3 AF XY: 0.00266 AC XY: 356AN XY: 134082
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GnomAD4 exome AF: 0.00297 AC: 4331AN: 1459778Hom.: 13 Cov.: 31 AF XY: 0.00297 AC XY: 2155AN XY: 726130
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GnomAD4 genome AF: 0.00224 AC: 342AN: 152342Hom.: 0 Cov.: 33 AF XY: 0.00204 AC XY: 152AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
CELSR1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at