rs9615362

Variant names:

• chr22-46399244-C-A
• rs9615362
• NM_001378328.1:c.5412+473G>T

Your query was ambiguous. Multiple possible variants found:

• chr22-46399244-C-A
• chr22-46399244-C-T

Variant summary

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

The NM_001378328.1(CELSR1):​c.5412+473G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,042 control chromosomes in the GnomAD database, including 8,033 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 0.23 (8033 hom., cov: 32)
• Consequence: CELSR1 NM_001378328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR1	NM_001378328.1	c.5412+473G>T		intron_variant	Intron 10 of 34	ENST00000674500.2	NP_001365257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR1	ENST00000674500.2	c.5412+473G>T		intron_variant	Intron 10 of 34		NM_001378328.1	ENSP00000501367.2
CELSR1	ENST00000262738.9	c.5412+473G>T		intron_variant	Intron 10 of 34	1		ENSP00000262738.3
CELSR1	ENST00000674359.1	c.423+473G>T		intron_variant	Intron 3 of 9			ENSP00000501512.1
CELSR1	ENST00000674341.1	n.489+473G>T		intron_variant	Intron 2 of 18

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35274 AN: 151924 Hom.: 7995 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.0153

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.233 AC: 35364 AN: 152042 Hom.: 8033 Cov.: 32 AF XY: 0.226 AC XY: 16829 AN XY: 74372

African (AFR) AF: 0.595 AC: 24651 AN: 41406

American (AMR) AF: 0.117 AC: 1792 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 438 AN: 3468

East Asian (EAS) AF: 0.0151 AC: 78 AN: 5168

South Asian (SAS) AF: 0.0828 AC: 399 AN: 4820

European-Finnish (FIN) AF: 0.0715 AC: 759 AN: 10608

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.0989 AC: 6722 AN: 67978

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.128 Hom.: 8374

Bravo AF: 0.249

Asia WGS AF: 0.0850 AC: 297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.093
DANN	Benign	0.29
PhyloP100		-1.2
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: rs9615362; hg19: chr22-46795141;