rs4970833

Positions:

• chr1-109262024-G-A
• chr1-109262024-G-C
• chr1-109262024-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001408.3(CELSR2):​c.4386+128G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,102,024 control chromosomes in the GnomAD database, including 108,268 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 0.36 (11678 hom., cov: 33)
  • Exomes 𝑓: 0.44 (96590 hom.)
• Consequence: CELSR2 NM_001408.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.4386+128G>A		intron_variant		ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4	c.4386+128G>A		intron_variant		1	NM_001408.3	ENSP00000271332	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 55034 AN: 152026 Hom.: 11676 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.508

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.412

GnomAD4 exome AF: 0.445 AC: 422231 AN: 949880 Hom.: 96590 AF XY: 0.445 AC XY: 213620 AN XY: 479566

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.498

Gnomad4 EAS exome AF: 0.487

Gnomad4 SAS exome AF: 0.402

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.454

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.362 AC: 55049 AN: 152144 Hom.: 11678 Cov.: 33 AF XY: 0.362 AC XY: 26883 AN XY: 74362

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.508

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.415

Alfa AF: 0.449 Hom.: 20399

Bravo AF: 0.356

Asia WGS AF: 0.443 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.4
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs4970833; hg19: chr1-109804646;