rs12740374

Positions:

• chr1-109274968-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.*919G>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 0.222 in 152,454 control chromosomes in the GnomAD database, including 3,965 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (3957 hom., cov: 32)
  • Exomes 𝑓: 0.19 (8 hom.)
• Consequence: CELSR2 NM_001408.3 3_prime_UTR
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: -0.174

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.*919G>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.*919G>T		3_prime_UTR_variant	34/34	1	NM_001408.3	ENSP00000271332	P1
CELSR2	ENST00000498157.1	n.3041G>T		non_coding_transcript_exon_variant	5/5	2

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33705 AN: 151890 Hom.: 3948 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.187 AC: 83 AN: 444 Hom.: 8 Cov.: 0 AF XY: 0.199 AC XY: 55 AN XY: 276

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.222 AC: 33745 AN: 152010 Hom.: 3957 Cov.: 32 AF XY: 0.223 AC XY: 16573 AN XY: 74328

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0620

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.212

Alfa AF: 0.211 Hom.: 4612

Bravo AF: 0.222

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Low density lipoprotein cholesterol level quantitative trait locus 6 Other:1

association, no assertion criteria provided

literature only

OMIM

Aug 05, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.0
DANN	Benign	0.55

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: rs12740374; hg19: chr1-109817590; COSMIC: COSV54781525; COSMIC: COSV54781525;