NM_001408.3:c.7927-20C>T

Variant names:

• chr1-109272258-C-T
• rs4970834
• NM_001408.3:c.7927-20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001408.3(CELSR2):​c.7927-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 1,550,728 control chromosomes in the GnomAD database, including 27,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3739 hom., cov: 33)
  • Exomes 𝑓: 0.18 (24109 hom.)
• Consequence: CELSR2 NM_001408.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.871
• Publications: 72 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-109272258-C-T is Benign according to our data. Variant chr1-109272258-C-T is described in ClinVar as Benign. ClinVar VariationId is 1601365.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001408.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR2	NM_001408.3	MANE Select	c.7927-20C>T		intron	N/A	NP_001399.1	Q9HCU4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CELSR2	ENST00000271332.4	TSL:1 MANE Select	c.7927-20C>T		intron	N/A	ENSP00000271332.3	Q9HCU4
	CELSR2	ENST00000489018.1	TSL:5	n.1619-20C>T		intron	N/A
	CELSR2	ENST00000498157.1	TSL:2	n.723-20C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31830 AN: 152092 Hom.: 3736 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.178

GnomAD2 exomes AF: 0.166 AC: 35062 AN: 211670 AF XY: 0.165

Gnomad AFR exome AF: 0.305

Gnomad AMR exome AF: 0.0819

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.0478

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.162

GnomAD4 exome AF: 0.180 AC: 251918 AN: 1398518 Hom.: 24109 Cov.: 33 AF XY: 0.179 AC XY: 123063 AN XY: 688156

African (AFR) AF: 0.313 AC: 9877 AN: 31530

American (AMR) AF: 0.0862 AC: 3079 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2467 AN: 22752

East Asian (EAS) AF: 0.0532 AC: 2058 AN: 38658

South Asian (SAS) AF: 0.160 AC: 12458 AN: 77988

European-Finnish (FIN) AF: 0.192 AC: 9924 AN: 51558

Middle Eastern (MID) AF: 0.128 AC: 705 AN: 5508

European-Non Finnish (NFE) AF: 0.187 AC: 201174 AN: 1077256

Other (OTH) AF: 0.177 AC: 10176 AN: 57560

GnomAD4 genome AF: 0.209 AC: 31859 AN: 152210 Hom.: 3739 Cov.: 33 AF XY: 0.208 AC XY: 15500 AN XY: 74408

African (AFR) AF: 0.311 AC: 12910 AN: 41506

American (AMR) AF: 0.124 AC: 1892 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3472

East Asian (EAS) AF: 0.0478 AC: 248 AN: 5184

South Asian (SAS) AF: 0.155 AC: 746 AN: 4822

European-Finnish (FIN) AF: 0.205 AC: 2177 AN: 10600

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12865 AN: 67992

Other (OTH) AF: 0.176 AC: 373 AN: 2116

Alfa AF: 0.188 Hom.: 8821

Bravo AF: 0.209

Asia WGS AF: 0.103 AC: 360 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		-0.87
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: rs4970834; hg19: chr1-109814880; COSMIC: COSV54766966;