rs3788706

Variant names:

• chr22-46473273-G-A
• rs3788706
• NM_001378328.1:c.3545-8928C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-46473273-G-A
• chr22-46473273-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001378328.1(CELSR1):​c.3545-8928C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,128 control chromosomes in the GnomAD database, including 1,668 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 0.14 (1668 hom., cov: 32)
• Consequence: CELSR1 NM_001378328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR1	NM_001378328.1	c.3545-8928C>T		intron_variant	Intron 1 of 34	ENST00000674500.2	NP_001365257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR1	ENST00000674500.2	c.3545-8928C>T		intron_variant	Intron 1 of 34		NM_001378328.1	ENSP00000501367.2
CELSR1	ENST00000262738.9	c.3545-8928C>T		intron_variant	Intron 1 of 34	1		ENSP00000262738.3
CELSR1	ENST00000454637.2	c.3545-8928C>T		intron_variant	Intron 1 of 2	1		ENSP00000414689.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21884 AN: 152010 Hom.: 1668 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.144 AC: 21912 AN: 152128 Hom.: 1668 Cov.: 32 AF XY: 0.141 AC XY: 10497 AN XY: 74362

African (AFR) AF: 0.142 AC: 5910 AN: 41492

American (AMR) AF: 0.211 AC: 3222 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 398 AN: 3472

East Asian (EAS) AF: 0.242 AC: 1248 AN: 5148

South Asian (SAS) AF: 0.110 AC: 531 AN: 4810

European-Finnish (FIN) AF: 0.102 AC: 1080 AN: 10618

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9074 AN: 67990

Other (OTH) AF: 0.166 AC: 349 AN: 2102

Alfa AF: 0.134 Hom.: 841

Bravo AF: 0.154

Asia WGS AF: 0.178 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.0
DANN	Benign	0.41
PhyloP100		0.0020
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: rs3788706; hg19: chr22-46869170;