Variant rs4970834 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001408.3(CELSR2):c.7927-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,550,728 control chromosomes in the GnomAD database, including 27,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3739 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24109 hom. )

Consequence

CELSR2
NM_001408.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.871

Variant links:

Genes affected

CELSR2 (HGNC:3231): (cadherin EGF LAG seven-pass G-type receptor 2) 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. The specific function of this particular member has not been determined. [provided by RefSeq, Jul 2008]

CELSR2 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 (BayesDel_noAF=-0.74).

BP6

Variant 1-109272258-C-T is Benign according to our data. Variant chr1-109272258-C-T is described in ClinVar as [Benign]. Clinvar id is 1601365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELSR2	NM_001408.3 linkuse as main transcript	c.7927-20C>T		intron_variant		ENST00000271332.4

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
CELSR2	ENST00000271332.4 linkuse as main transcript	c.7927-20C>T	intron_variant	1	NM_001408.3	P1
CELSR2	ENST00000489018.1 linkuse as main transcript	n.1619-20C>T	intron_variant, non_coding_transcript_variant	5
CELSR2	ENST00000498157.1 linkuse as main transcript	n.723-20C>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31830

AN:

152092

Hom.:

3736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.311

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.0485

Gnomad SAS

AF:

0.155

Gnomad FIN

AF:

0.205

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.178

GnomAD3 exomes

AF:

0.166

AC:

35062

AN:

211670

Hom.:

3437

AF XY:

0.165

AC XY:

18812

AN XY:

113898

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.0819

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.0478

Gnomad SAS exome

AF:

0.159

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.185

Gnomad OTH exome

AF:

0.162

GnomAD4 exome

AF:

0.180

AC:

251918

AN:

1398518

Hom.:

24109

Cov.:

AF XY:

0.179

AC XY:

123063

AN XY:

688156

show subpopulations

Gnomad4 AFR exome

AF:

0.313

Gnomad4 AMR exome

AF:

0.0862

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.0532

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.192

Gnomad4 NFE exome

AF:

0.187

Gnomad4 OTH exome

AF:

0.177

GnomAD4 genome

AF:

0.209

AC:

31859

AN:

152210

Hom.:

3739

Cov.:

AF XY:

0.208

AC XY:

15500

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.311

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.0478

Gnomad4 SAS

AF:

0.155

Gnomad4 FIN

AF:

0.205

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.179

Hom.:

3757

Bravo

AF:

0.209

Asia WGS

AF:

0.103

AC:

360

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.72

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