22-46364139-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001378328.1(CELSR1):c.8892G>A(p.Ser2964Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000367 in 1,607,532 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CELSR1
NM_001378328.1 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.95

Publications

1 publications found

Variant links:

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]

CELSR1 Gene-Disease associations (from GenCC):

lymphatic malformation 9
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
neural tube defects, susceptibility to
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina
epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
hydrops fetalis
Inheritance: AD Classification: LIMITED Submitted by: G2P
genetic developmental and epileptic encephalopathy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

CELSR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 22-46364139-C-T is Benign according to our data. Variant chr22-46364139-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3036476.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000601 (9/149828) while in subpopulation SAS AF = 0.000207 (1/4836). AF 95% confidence interval is 0.0000496. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378328.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR1	NM_001378328.1	MANE Select	c.8892G>A	p.Ser2964Ser	synonymous	Exon 34 of 35	NP_001365257.1	A0A6I8PRU0
	CELSR1	NM_014246.4		c.8892G>A	p.Ser2964Ser	synonymous	Exon 34 of 35	NP_055061.1	Q9NYQ6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CELSR1	ENST00000674500.2	MANE Select	c.8892G>A	p.Ser2964Ser	synonymous	Exon 34 of 35	ENSP00000501367.2	A0A6I8PRU0
CELSR1	ENST00000262738.9	TSL:1	c.8892G>A	p.Ser2964Ser	synonymous	Exon 34 of 35	ENSP00000262738.3	Q9NYQ6-1
CELSR1	ENST00000473624.2	TSL:1	c.645G>A	p.Ser215Ser	synonymous	Exon 5 of 5	ENSP00000501353.1	A0A6I8PL36

Frequencies

GnomAD3 genomes

AF:

0.0000601

AC:

AN:

149828

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000805

AC:

AN:

248568

AF XY:

0.0000814

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000219

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000343

AC:

AN:

1457704

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

725394

show subpopulations

African (AFR)

AF:

0.000221

AC:

AN:

31644

American (AMR)

AF:

0.000135

AC:

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51992

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111584

Other (OTH)

AF:

0.0000166

AC:

AN:

60142

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000601

AC:

AN:

149828

Hom.:

Cov.:

AF XY:

0.0000410

AC XY:

AN XY:

73224

show subpopulations

African (AFR)

AF:

0.000128

AC:

AN:

39166

American (AMR)

AF:

0.00

AC:

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000192

AC:

AN:

5200

South Asian (SAS)

AF:

0.000207

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000529

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CELSR1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.018

(source)

DANN

Benign

0.42

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over