3-48639758-G-A

Position:

chr3-48639758-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001407.3(CELSR3):c.9827C>T(p.Pro3276Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00771 in 1,613,788 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0062 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0079 ( 87 hom. )

Consequence

CELSR3
NM_001407.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.12

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:

CELSR3 (HGNC:):

CELSR3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051828325).

BP6

Variant 3-48639758-G-A is Benign according to our data. Variant chr3-48639758-G-A is described in ClinVar as [Benign]. Clinvar id is 770700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00787 (11508/1461480) while in subpopulation MID AF= 0.039 (225/5766). AF 95% confidence interval is 0.0348. There are 87 homozygotes in gnomad4_exome. There are 5767 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 939 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR3	NM_001407.3 linkuse as main transcript	c.9827C>T	p.Pro3276Leu	missense_variant	34/35	ENST00000164024.5	NP_001398.2	Q9NYQ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CELSR3	ENST00000164024.5 linkuse as main transcript	c.9827C>T	p.Pro3276Leu	missense_variant	34/35	1	NM_001407.3	ENSP00000164024.4	Q9NYQ7-1
CELSR3	ENST00000461362.5 linkuse as main transcript	n.1915C>T		non_coding_transcript_exon_variant	7/8	5
CELSR3	ENST00000498057.1 linkuse as main transcript	n.3579C>T		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.00618

AC:

940

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0478

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00795

Gnomad OTH

AF:

0.00862

GnomAD3 exomes

AF:

0.00812

AC:

2033

AN:

250300

Hom.:

AF XY:

0.00836

AC XY:

1135

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.000928

Gnomad AMR exome

AF:

0.00642

Gnomad ASJ exome

AF:

0.0478

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00595

Gnomad FIN exome

AF:

0.00360

Gnomad NFE exome

AF:

0.00856

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.00787

AC:

11508

AN:

1461480

Hom.:

Cov.:

AF XY:

0.00793

AC XY:

5767

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00149

Gnomad4 AMR exome

AF:

0.00655

Gnomad4 ASJ exome

AF:

0.0499

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00599

Gnomad4 FIN exome

AF:

0.00409

Gnomad4 NFE exome

AF:

0.00744

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00617

AC:

939

AN:

152308

Hom.:

Cov.:

AF XY:

0.00595

AC XY:

443

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.0478

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.00797

Gnomad4 OTH

AF:

0.00853

Alfa

AF:

0.00946

Hom.:

Bravo

AF:

0.00673

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00872

AC:

ExAC

AF:

0.00744

AC:

902

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0109

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	CELSR3: BS1, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

CELSR3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Benign

-0.13

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0052

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.012

Vest4

0.46

MVP

0.47

MPC

0.30

ClinPred

0.075

GERP RS

4.5

Varity_R

0.16

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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