chr22-46364218-G-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001378328.1(CELSR1):c.8813C>A(p.Pro2938Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000714 in 1,610,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
CELSR1
NM_001378328.1 missense
NM_001378328.1 missense
Scores
1
12
6
Clinical Significance
Conservation
PhyloP100: 6.16
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 -7 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1709106).
BP6
?
Variant 22-46364218-G-T is Benign according to our data. Variant chr22-46364218-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2653306.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.
BS2
?
High AC in GnomAd at 40 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CELSR1 | NM_001378328.1 | c.8813C>A | p.Pro2938Gln | missense_variant | 34/35 | ENST00000674500.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CELSR1 | ENST00000674500.2 | c.8813C>A | p.Pro2938Gln | missense_variant | 34/35 | NM_001378328.1 | A2 | ||
CELSR1 | ENST00000262738.9 | c.8813C>A | p.Pro2938Gln | missense_variant | 34/35 | 1 | P4 | ||
CELSR1 | ENST00000473624.2 | c.566C>A | p.Pro189Gln | missense_variant | 5/5 | 1 | |||
CELSR1 | ENST00000674159.1 | n.2256C>A | non_coding_transcript_exon_variant | 10/11 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000236 AC: 58AN: 245306Hom.: 0 AF XY: 0.000165 AC XY: 22AN XY: 133666
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GnomAD4 exome AF: 0.0000514 AC: 75AN: 1458596Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 39AN XY: 725734
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GnomAD4 genome ? AF: 0.000263 AC: 40AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.000363 AC XY: 27AN XY: 74360
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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 | Ambry Genetics | May 26, 2022 | The c.8813C>A (p.P2938Q) alteration is located in exon 34 (coding exon 34) of the CELSR1 gene. This alteration results from a C to A substitution at nucleotide position 8813, causing the proline (P) at amino acid position 2938 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | CELSR1: BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Uncertain
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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