1-109275908-C-T

Variant names:

• chr1-109275908-C-T
• rs646776
• NM_001408.3:c.*1859C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001408.3(CELSR2):​c.*1859C>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,172 control chromosomes in the GnomAD database, including 43,007 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 (43007 hom., cov: 33)
• Consequence: CELSR2 NM_001408.3 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44
• Publications: 349 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 -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 = 0.914 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.*1859C>T		downstream_gene_variant		ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4	c.*1859C>T		downstream_gene_variant		1	NM_001408.3	ENSP00000271332.3

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113691 AN: 152054 Hom.: 42991 Cov.: 33

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.830

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.765

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.748 AC: 113752 AN: 152172 Hom.: 43007 Cov.: 33 AF XY: 0.747 AC XY: 55622 AN XY: 74418

African (AFR) AF: 0.647 AC: 26844 AN: 41506

American (AMR) AF: 0.777 AC: 11886 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 2879 AN: 3468

East Asian (EAS) AF: 0.936 AC: 4845 AN: 5174

South Asian (SAS) AF: 0.754 AC: 3637 AN: 4824

European-Finnish (FIN) AF: 0.778 AC: 8251 AN: 10600

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52917 AN: 67984

Other (OTH) AF: 0.767 AC: 1619 AN: 2112

Alfa AF: 0.773 Hom.: 200270

Bravo AF: 0.742

Asia WGS AF: 0.839 AC: 2918 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	0.089
DANN	Benign	0.48
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs646776; hg19: chr1-109818530;