rs6008817

Positions:

• chr22-46418774-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.4612-7015G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,178 control chromosomes in the GnomAD database, including 12,925 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 0.35 (12925 hom., cov: 33)
• Consequence: CELSR1 NM_001378328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 (AFR) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CELSR1	NM_001378328.1	c.4612-7015G>A		intron_variant		ENST00000674500.2	NP_001365257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CELSR1	ENST00000674500.2	c.4612-7015G>A		intron_variant			NM_001378328.1	ENSP00000501367	A2
CELSR1	ENST00000262738.9	c.4612-7015G>A		intron_variant		1		ENSP00000262738	P4

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52619 AN: 152060 Hom.: 12881 Cov.: 33

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0163

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.346 AC: 52711 AN: 152178 Hom.: 12925 Cov.: 33 AF XY: 0.335 AC XY: 24946 AN XY: 74384

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0162

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.290

Alfa AF: 0.245 Hom.: 10231

Bravo AF: 0.362

Asia WGS AF: 0.131 AC: 456 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	0.56
DANN	Benign	0.83

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: rs6008817; hg19: chr22-46814671;