22-46364043-G-C
Variant names:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001378328.1(CELSR1):c.8988C>G(p.Ala2996Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00193 in 1,611,740 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0082 ( 18 hom., cov: 33)
Exomes 𝑓: 0.0013 ( 38 hom. )
Consequence
CELSR1
NM_001378328.1 synonymous
NM_001378328.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.51
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 -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 22-46364043-G-C is Benign according to our data. Variant chr22-46364043-G-C is described in ClinVar as [Benign]. Clinvar id is 720966.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2.51 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00821 (1251/152296) while in subpopulation AFR AF= 0.0277 (1151/41558). AF 95% confidence interval is 0.0264. There are 18 homozygotes in gnomad4. There are 591 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1251 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CELSR1 | NM_001378328.1 | c.8988C>G | p.Ala2996Ala | synonymous_variant | Exon 34 of 35 | ENST00000674500.2 | NP_001365257.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CELSR1 | ENST00000674500.2 | c.8988C>G | p.Ala2996Ala | synonymous_variant | Exon 34 of 35 | NM_001378328.1 | ENSP00000501367.2 | |||
| CELSR1 | ENST00000262738.9 | c.8988C>G | p.Ala2996Ala | synonymous_variant | Exon 34 of 35 | 1 | ENSP00000262738.3 | |||
| CELSR1 | ENST00000473624.2 | c.741C>G | p.Ala247Ala | synonymous_variant | Exon 5 of 5 | 1 | ENSP00000501353.1 | |||
| CELSR1 | ENST00000674159.1 | n.2431C>G | non_coding_transcript_exon_variant | Exon 10 of 11 |
Frequencies
GnomAD3 genomes 0.00823 AC: 1252AN: 152178Hom.: 18 Cov.: 33
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GnomAD3 exomes AF: 0.00294 AC: 721AN: 245134Hom.: 10 AF XY: 0.00265 AC XY: 354AN XY: 133760
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GnomAD4 exome AF: 0.00128 AC: 1867AN: 1459444Hom.: 38 Cov.: 31 AF XY: 0.00133 AC XY: 968AN XY: 725944
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GnomAD4 genome 0.00821 AC: 1251AN: 152296Hom.: 18 Cov.: 33 AF XY: 0.00794 AC XY: 591AN XY: 74462
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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
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Dec 31, 2019
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
CELSR1-related disorder Benign:1
Jan 02, 2020
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing
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). -
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