chr22-46509636-T-C

Position:

• chr22-46509636-T-C

Variant summary

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

The NM_001378328.1(CELSR1):​c.3544+23991A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,040 control chromosomes in the GnomAD database, including 32,912 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 0.66 (32912 hom., cov: 32)
• Consequence: CELSR1 NM_001378328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR1	NM_001378328.1	c.3544+23991A>G		intron_variant		ENST00000674500.2	NP_001365257.1
CELSR1	NM_014246.4	c.3544+23991A>G		intron_variant			NP_055061.1
CELSR1	XM_011530553.2	c.3544+23991A>G		intron_variant			XP_011528855.1
CELSR1	XM_047441624.1	c.3544+23991A>G		intron_variant			XP_047297580.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELSR1	ENST00000674500.2	c.3544+23991A>G		intron_variant			NM_001378328.1	ENSP00000501367	A2
CELSR1	ENST00000262738.9	c.3544+23991A>G		intron_variant		1		ENSP00000262738	P4
CELSR1	ENST00000454637.2	c.3544+23991A>G		intron_variant		1		ENSP00000414689

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99556 AN: 151922 Hom.: 32876 Cov.: 32

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.717

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.655 AC: 99644 AN: 152040 Hom.: 32912 Cov.: 32 AF XY: 0.657 AC XY: 48862 AN XY: 74324

Gnomad4 AFR AF: 0.558

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.652

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.663

Alfa AF: 0.679 Hom.: 69675

Bravo AF: 0.648

Asia WGS AF: 0.648 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.68
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: rs3788723; hg19: chr22-46905533;