1-109272630-A-G

Variant names:

• chr1-109272630-A-G
• rs611917
• NM_001408.3:c.8055-10A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001408.3(CELSR2):​c.8055-10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,610,362 control chromosomes in the GnomAD database, including 76,647 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7667 hom., cov: 32)
  • Exomes 𝑓: 0.30 (68980 hom.)
• Consequence: CELSR2 NM_001408.3 intron
• Scores: Splicing: ADA: 0.0001355
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.677
• Publications: 59 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-109272630-A-G is Benign according to our data. Variant chr1-109272630-A-G is described in ClinVar as Benign. ClinVar VariationId is 1530644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.8055-10A>G		intron_variant	Intron 29 of 33	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4	c.8055-10A>G		intron_variant	Intron 29 of 33	1	NM_001408.3	ENSP00000271332.3
CELSR2	ENST00000489018.1	n.1971A>G		non_coding_transcript_exon_variant	Exon 5 of 9	5
CELSR2	ENST00000498157.1	n.851-10A>G		intron_variant	Intron 3 of 4	2

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47126 AN: 151878 Hom.: 7656 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.294

GnomAD2 exomes AF: 0.282 AC: 69921 AN: 247816 AF XY: 0.283

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.239

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.0648

Gnomad FIN exome AF: 0.338

Gnomad NFE exome AF: 0.316

Gnomad OTH exome AF: 0.276

GnomAD4 exome AF: 0.304 AC: 442987 AN: 1458364 Hom.: 68980 Cov.: 33 AF XY: 0.302 AC XY: 219069 AN XY: 725640

African (AFR) AF: 0.336 AC: 11243 AN: 33424

American (AMR) AF: 0.245 AC: 10949 AN: 44638

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 7880 AN: 26060

East Asian (EAS) AF: 0.0692 AC: 2745 AN: 39678

South Asian (SAS) AF: 0.267 AC: 23025 AN: 86194

European-Finnish (FIN) AF: 0.328 AC: 17280 AN: 52706

Middle Eastern (MID) AF: 0.234 AC: 1346 AN: 5756

European-Non Finnish (NFE) AF: 0.316 AC: 350466 AN: 1109628

Other (OTH) AF: 0.299 AC: 18053 AN: 60280

GnomAD4 genome AF: 0.310 AC: 47164 AN: 151998 Hom.: 7667 Cov.: 32 AF XY: 0.310 AC XY: 23032 AN XY: 74302

African (AFR) AF: 0.336 AC: 13926 AN: 41468

American (AMR) AF: 0.274 AC: 4192 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1025 AN: 3468

East Asian (EAS) AF: 0.0639 AC: 331 AN: 5180

South Asian (SAS) AF: 0.263 AC: 1264 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3656 AN: 10578

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.318 AC: 21626 AN: 67904

Other (OTH) AF: 0.292 AC: 614 AN: 2106

Alfa AF: 0.310 Hom.: 5089

Bravo AF: 0.307

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 30, 2025

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

CELSR2-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.86
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00014
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs611917; hg19: chr1-109815252; COSMIC: COSV54773351;