dbSNP rs7528419: CELSR2:c.*521A>G (chr1-109274570-A-G) – 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.*521A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 163,362 control chromosomes in the GnomAD database, including 4,378 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 0.23 ( 4150 hom., cov: 32)

Exomes 𝑓: 0.19 ( 228 hom. )

Consequence

CELSR2
NM_001408.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.543

Publications

153 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:

Genome browser will be placed here

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=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3 link	c.*521A>G		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.*521A>G		3_prime_UTR_variant	Exon 34 of 34	1	NM_001408.3	ENSP00000271332.3		Q9HCU4
CELSR2	ENST00000498157.1 link	n.2643A>G		non_coding_transcript_exon_variant	Exon 5 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34583

AN:

152002

Hom.:

4141

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.326

Gnomad AMR

AF:

0.212

Gnomad ASJ

AF:

0.170

Gnomad EAS

AF:

0.0633

Gnomad SAS

AF:

0.244

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.218

GnomAD4 exome

AF:

0.186

AC:

2095

AN:

11242

Hom.:

228

Cov.:

AF XY:

0.186

AC XY:

1086

AN XY:

5846

show subpopulations

African (AFR)

AF:

0.267

AC:

AN:

172

American (AMR)

AF:

0.190

AC:

265

AN:

1394

Ashkenazi Jewish (ASJ)

AF:

0.205

AC:

AN:

176

East Asian (EAS)

AF:

0.0679

AC:

AN:

604

South Asian (SAS)

AF:

0.221

AC:

172

AN:

780

European-Finnish (FIN)

AF:

0.175

AC:

111

AN:

636

Middle Eastern (MID)

AF:

0.0357

AC:

AN:

European-Non Finnish (NFE)

AF:

0.190

AC:

1310

AN:

6908

Other (OTH)

AF:

0.208

AC:

113

AN:

544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.228

AC:

34626

AN:

152120

Hom.:

4150

Cov.:

AF XY:

0.228

AC XY:

16980

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.268

AC:

11119

AN:

41492

American (AMR)

AF:

0.212

AC:

3244

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

588

AN:

3468

East Asian (EAS)

AF:

0.0631

AC:

325

AN:

5150

South Asian (SAS)

AF:

0.244

AC:

1178

AN:

4824

European-Finnish (FIN)

AF:

0.221

AC:

2347

AN:

10612

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15041

AN:

67968

Other (OTH)

AF:

0.216

AC:

456

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1396

2791

4187

5582

6978

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.219

Hom.:

15013

Bravo

AF:

0.229

Asia WGS

AF:

0.154

AC:

534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.46

(source)

DANN

Benign

0.45

PhyloP100

-0.54

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over