22-46504565-C-T

Variant summary

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

The NM_001378328.1(CELSR1):c.3544+29062G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.818 in 150,534 control chromosomes in the GnomAD database, including 50,543 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 0.82 (50543 hom., cov: 28)
• Consequence: CELSR1 NM_001378328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

Genes affected

CELSR1 (HGNC:1850): (cadherin EGF LAG seven-pass G-type receptor 1) 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. This particular member is a developmentally regulated, neural-specific gene which plays an unspecified role in early embryogenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CELSR1	NM_001378328.1	c.3544+29062G>A		intron_variant		ENST00000674500.2
CELSR1	NM_014246.4	c.3544+29062G>A		intron_variant
CELSR1	XM_011530553.2	c.3544+29062G>A		intron_variant
CELSR1	XM_047441624.1	c.3544+29062G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CELSR1	ENST00000674500.2	c.3544+29062G>A		intron_variant			NM_001378328.1	A2
CELSR1	ENST00000262738.9	c.3544+29062G>A		intron_variant		1		P4
CELSR1	ENST00000454637.2	c.3544+29062G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 123089 AN: 150418 Hom.: 50511 Cov.: 28

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.787

Gnomad OTH AF: 0.824

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

GnomAD4 genome AF: 0.818 AC: 123172 AN: 150534 Hom.: 50543 Cov.: 28 AF XY: 0.822 AC XY: 60240 AN XY: 73324

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.843

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.983

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.787

Gnomad4 OTH AF: 0.822

Alfa AF: 0.792 Hom.: 96609

Bravo AF: 0.819

Asia WGS AF: 0.858 AC: 2987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.68

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: rs5768857; hg19: chr22-46900462;