1-109264661-A-T

Variant names:

• chr1-109264661-A-T
• rs6657811
• NM_001408.3:c.5464+33A>T

Variant summary

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

The NM_001408.3(CELSR2):​c.5464+33A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,600,146 control chromosomes in the GnomAD database, including 12,076 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 0.12 (1197 hom., cov: 33)
  • Exomes 𝑓: 0.12 (10879 hom.)
• Consequence: CELSR2 NM_001408.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711
• Publications: 33 publications found

Genes affected

CELSR2 (HGNC:3231): (cadherin EGF LAG seven-pass G-type receptor 2) 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. The specific function of this particular member has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CELSR2	NM_001408.3	c.5464+33A>T		intron_variant	Intron 11 of 33	ENST00000271332.4	NP_001399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CELSR2	ENST00000271332.4	c.5464+33A>T		intron_variant	Intron 11 of 33	1	NM_001408.3	ENSP00000271332.3

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17944 AN: 152144 Hom.: 1194 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0887

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0885

Gnomad FIN AF: 0.0966

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.101 AC: 24986 AN: 247416 AF XY: 0.102

Gnomad AFR exome AF: 0.140

Gnomad AMR exome AF: 0.0596

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.00207

Gnomad FIN exome AF: 0.0973

Gnomad NFE exome AF: 0.126

Gnomad OTH exome AF: 0.0954

GnomAD4 exome AF: 0.119 AC: 172544 AN: 1447884 Hom.: 10879 Cov.: 35 AF XY: 0.118 AC XY: 84563 AN XY: 717236

African (AFR) AF: 0.145 AC: 4828 AN: 33268

American (AMR) AF: 0.0629 AC: 2797 AN: 44482

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 3393 AN: 25780

East Asian (EAS) AF: 0.00221 AC: 87 AN: 39314

South Asian (SAS) AF: 0.0901 AC: 7728 AN: 85724

European-Finnish (FIN) AF: 0.0965 AC: 5116 AN: 52992

Middle Eastern (MID) AF: 0.0803 AC: 460 AN: 5726

European-Non Finnish (NFE) AF: 0.128 AC: 141178 AN: 1100884

Other (OTH) AF: 0.117 AC: 6957 AN: 59714

GnomAD4 genome AF: 0.118 AC: 17967 AN: 152262 Hom.: 1197 Cov.: 33 AF XY: 0.115 AC XY: 8583 AN XY: 74458

African (AFR) AF: 0.140 AC: 5819 AN: 41548

American (AMR) AF: 0.0885 AC: 1354 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3470

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.0884 AC: 426 AN: 4820

European-Finnish (FIN) AF: 0.0966 AC: 1024 AN: 10604

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8493 AN: 68018

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.0787 Hom.: 110

Bravo AF: 0.121

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.65
DANN	Benign	0.68
PhyloP100		-0.71
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: rs6657811; hg19: chr1-109807283;