1-109275684-G-T

Position:

• chr1-109275684-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.75 (42979 hom., cov: 34)
  • Exomes 𝑓: 1.0 (8 hom.)
• Consequence: CELSR2 NM_001408.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-109275684-G-T is Benign according to our data. Variant chr1-109275684-G-T is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.*1635G>T		3_prime_UTR_variant	34/34	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4	c.*1635G>T		3_prime_UTR_variant	34/34	1	NM_001408.3	ENSP00000271332.3

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113682 AN: 152098 Hom.: 42963 Cov.: 34

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: 16 AN: 16 Hom.: 8 Cov.: 0 AF XY: 1.00 AC XY: 10 AN XY: 10

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.747 AC: 113743 AN: 152216 Hom.: 42979 Cov.: 34 AF XY: 0.747 AC XY: 55627 AN XY: 74440

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.777

Gnomad4 ASJ AF: 0.830

Gnomad4 EAS AF: 0.934

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.768

Alfa AF: 0.781 Hom.: 55050

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
DANN	Benign	0.76
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs629301; hg19: chr1-109818306;