chr1-109275216-T-C

Position:

• chr1-109275216-T-C

Variant summary

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

The ENST00000271332.4(CELSR2):​c.*1167T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,176 control chromosomes in the GnomAD database, including 43,737 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 (43725 hom., cov: 33)
  • Exomes 𝑓: 0.93 (12 hom.)
• Consequence: CELSR2 ENST00000271332.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.380

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=-0.49).
• 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/exons	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.*1167T>C		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.*1167T>C		3_prime_UTR_variant	34/34	1	NM_001408.3	ENSP00000271332	P1
CELSR2	ENST00000498157.1	n.3289T>C		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114650 AN: 152030 Hom.: 43708 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.936

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.780

GnomAD4 exome AF: 0.929 AC: 26 AN: 28 Hom.: 12 Cov.: 0 AF XY: 0.900 AC XY: 18 AN XY: 20

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.950

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.754 AC: 114711 AN: 152148 Hom.: 43725 Cov.: 33 AF XY: 0.754 AC XY: 56077 AN XY: 74384

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.936

Gnomad4 SAS AF: 0.756

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.782

Alfa AF: 0.789 Hom.: 88511

Bravo AF: 0.750

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	-0.49
CADD	Benign	12
DANN	Benign	0.83
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: rs660240; hg19: chr1-109817838;