Variant 3-48640188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001407.3(CELSR3):c.9397G>A(p.Ala3133Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000611 in 1,612,704 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

CELSR3
NM_001407.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.292

Variant links:

Genes affected

CELSR3 (HGNC:3230): (cadherin EGF LAG seven-pass G-type receptor 3) This gene belongs to the flamingo subfamily, which is included in the cadherin superfamily. The flamingo cadherins consist of nonclassic-type cadherins that do not interact with catenins. They are plasma membrane proteins containing seven epidermal growth factor-like repeats, nine cadherin domains and two laminin A G-type repeats in their ectodomain. They also have seven transmembrane domains, a characteristic feature of their subfamily. The encoded protein may be involved in the regulation of contact-dependent neurite growth and may play a role in tumor formation. [provided by RefSeq, Jun 2013]

CELSR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003721714).

BP6

Variant 3-48640188-C-T is Benign according to our data. Variant chr3-48640188-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3053810.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 83 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR3	NM_001407.3 linkuse as main transcript	c.9397G>A	p.Ala3133Thr	missense_variant	34/35	ENST00000164024.5	NP_001398.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELSR3	ENST00000164024.5 linkuse as main transcript	c.9397G>A	p.Ala3133Thr	missense_variant	34/35	1	NM_001407.3	ENSP00000164024	P1	Q9NYQ7-1
CELSR3	ENST00000461362.5 linkuse as main transcript	n.1485G>A		non_coding_transcript_exon_variant	7/8	5
CELSR3	ENST00000498057.1 linkuse as main transcript	n.3149G>A		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000555

AC:

137

AN:

246664

Hom.:

AF XY:

0.000432

AC XY:

AN XY:

134392

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000610

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000618

AC:

902

AN:

1460390

Hom.:

Cov.:

AF XY:

0.000567

AC XY:

412

AN XY:

726508

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000679

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000545

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000663

Hom.:

Bravo

AF:

0.000782

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000463

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CELSR3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 16, 2023

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

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.044

DANN

Benign

0.87

DEOGEN2

Benign

0.14

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.029

LIST_S2

Benign

0.35

M_CAP

Benign

0.037

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Benign

0.56

REVEL

Benign

0.086

Sift

Benign

0.88

Sift4G

Benign

0.79

Polyphen

0.0020

Vest4

0.055

MVP

0.32

MPC

0.25

ClinPred

0.014

GERP RS

-2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.034

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over