rs3788723

Variant names:

• chr22-46509636-T-C
• rs3788723
• NM_001378328.1:c.3544+23991A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

CELSR1 Gene-Disease associations (from GenCC):

• lymphatic malformation 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• neural tube defects, susceptibility to

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Illumina, Labcorp Genetics (formerly Invitae)
• epilepsy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hydrops fetalis

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001378328.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR1	NM_001378328.1	MANE Select	c.3544+23991A>G		intron	N/A	NP_001365257.1
	CELSR1	NM_014246.4		c.3544+23991A>G		intron	N/A	NP_055061.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR1	ENST00000674500.2	MANE Select	c.3544+23991A>G		intron	N/A	ENSP00000501367.2
	CELSR1	ENST00000262738.9	TSL:1	c.3544+23991A>G		intron	N/A	ENSP00000262738.3
	CELSR1	ENST00000454637.2	TSL:1	c.3544+23991A>G		intron	N/A	ENSP00000414689.2

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

African (AFR) AF: 0.558 AC: 23125 AN: 41438

American (AMR) AF: 0.692 AC: 10574 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2262 AN: 3470

East Asian (EAS) AF: 0.769 AC: 3967 AN: 5160

South Asian (SAS) AF: 0.555 AC: 2669 AN: 4810

European-Finnish (FIN) AF: 0.751 AC: 7954 AN: 10588

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.689 AC: 46862 AN: 67980

Other (OTH) AF: 0.663 AC: 1398 AN: 2108

Alfa AF: 0.672 Hom.: 105515

Bravo AF: 0.648

Asia WGS AF: 0.648 AC: 2256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.68
DANN	Benign	0.55
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3788723; hg19: chr22-46905533;