Genetic Variant NM_001408.3:c.*1635G>T (chr1-109275684-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001408.3(CELSR2):c.*1635G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,232 control chromosomes in the GnomAD database, including 42,987 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 42979 hom., cov: 34)

Exomes 𝑓: 1.0 ( 8 hom. )

Consequence

CELSR2
NM_001408.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.32

Publications

223 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3 link	c.*1635G>T		3_prime_UTR_variant	Exon 34 of 34	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4 link	c.*1635G>T		3_prime_UTR_variant	Exon 34 of 34	1	NM_001408.3	ENSP00000271332.3
CELSR2	ENST00000498157.1 link	n.*77G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113682

AN:

152098

Hom.:

42963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.646

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.776

Gnomad ASJ

AF:

0.830

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.754

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.779

Gnomad OTH

AF:

0.766

GnomAD4 exome

AF:

1.00

AC:

AN:

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

Age Distribution

Exome Hom

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:

0.747

AC:

113743

AN:

152216

Hom.:

42979

Cov.:

AF XY:

0.747

AC XY:

55627

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.645

AC:

26796

AN:

41512

American (AMR)

AF:

0.777

AC:

11881

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.830

AC:

2880

AN:

3470

East Asian (EAS)

AF:

0.934

AC:

4844

AN:

5186

South Asian (SAS)

AF:

0.754

AC:

3641

AN:

4826

European-Finnish (FIN)

AF:

0.779

AC:

8265

AN:

10614

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.779

AC:

52945

AN:

67996

Other (OTH)

AF:

0.768

AC:

1619

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1488

2976

4463

5951

7439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

856

1712

2568

3424

4280

<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:

0.773

Hom.:

151282

Bravo

AF:

0.742

Asia WGS

AF:

0.839

AC:

2917

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.23

(source)

DANN

Benign

0.76

PhyloP100

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over