chr3-48645117-C-T

Variant names:

Variant summary

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

The NM_001407.3(CELSR3):c.7890G>A(p.Met2630Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,606,028 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 51 hom. )

Consequence

CELSR3
NM_001407.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:2

Conservation

PhyloP100: 7.54

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011453748).

BP6

Variant 3-48645117-C-T is Benign according to our data. Variant chr3-48645117-C-T is described in ClinVar as [Benign]. Clinvar id is 40229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-48645117-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00177 (269/152350) while in subpopulation SAS AF= 0.019 (92/4834). AF 95% confidence interval is 0.0159. There are 2 homozygotes in gnomad4. There are 152 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 269 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR3	NM_001407.3 link	c.7890G>A	p.Met2630Ile	missense_variant	Exon 25 of 35	ENST00000164024.5	NP_001398.2	Q9NYQ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR3	ENST00000164024.5 link	c.7890G>A	p.Met2630Ile	missense_variant	Exon 25 of 35	1	NM_001407.3	ENSP00000164024.4		Q9NYQ7-1

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

270

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0190

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00393

AC:

976

AN:

248090

Hom.:

AF XY:

0.00500

AC XY:

674

AN XY:

134796

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0195

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.00171

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00245

AC:

3560

AN:

1453678

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

2196

AN XY:

721530

show subpopulations

Gnomad4 AFR exome

AF:

0.000929

Gnomad4 AMR exome

AF:

0.00169

Gnomad4 ASJ exome

AF:

0.00937

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0181

Gnomad4 FIN exome

AF:

0.000306

Gnomad4 NFE exome

AF:

0.00106

Gnomad4 OTH exome

AF:

0.00398

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152350

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0190

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00228

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00422

AC:

511

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.00300

EpiControl

AF:

0.00290

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 12, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Variant of unknown significance

Uncertain:1

Feb 01, 2013

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.77

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.39

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0050

Polyphen

0.99

Vest4

0.81

MutPred

0.55

Loss of disorder (P = 0.0676);

MVP

0.81

MPC

0.98

ClinPred

0.038

GERP RS

5.2

Varity_R

0.50

gMVP

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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