rs1520229

Variant names:

• chr16-65029726-G-A
• rs1520229
• NM_001797.4:c.-173+24078C>T

Variant summary

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

The NM_001797.4(CDH11):​c.-173+24078C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,052 control chromosomes in the GnomAD database, including 6,098 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 0.27 (6098 hom., cov: 32)
• Consequence: CDH11 NM_001797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.181
• Publications: 5 publications found

Genes affected

CDH11 (HGNC:1750): (cadherin 11) This gene encodes a type II classical cadherin from the cadherin superfamily, integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Mature cadherin proteins are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. Type II (atypical) cadherins are defined based on their lack of a HAV cell adhesion recognition sequence specific to type I cadherins. Expression of this particular cadherin in osteoblastic cell lines, and its upregulation during differentiation, suggests a specific function in bone development and maintenance. [provided by RefSeq, Jul 2008]

CDH11 Gene-Disease associations (from GenCC):

• Elsahy-Waters syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, G2P
• Teebi hypertelorism syndrome 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH11	NM_001797.4	c.-173+24078C>T		intron_variant	Intron 2 of 12	ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2	c.-173+24078C>T		intron_variant	Intron 2 of 13		NP_001295321.1
CDH11	NM_001330576.2	c.-151+24078C>T		intron_variant	Intron 2 of 11		NP_001317505.1
CDH11	XM_047433486.1	c.-151+24078C>T		intron_variant	Intron 2 of 11		XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603.9	c.-173+24078C>T		intron_variant	Intron 2 of 12	1	NM_001797.4	ENSP00000268603.4

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40567 AN: 151934 Hom.: 6096 Cov.: 32

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.280

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

GnomAD4 genome AF: 0.267 AC: 40576 AN: 152052 Hom.: 6098 Cov.: 32 AF XY: 0.260 AC XY: 19329 AN XY: 74318

African (AFR) AF: 0.135 AC: 5605 AN: 41510

American (AMR) AF: 0.265 AC: 4055 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1158 AN: 3472

East Asian (EAS) AF: 0.213 AC: 1098 AN: 5162

South Asian (SAS) AF: 0.208 AC: 1000 AN: 4812

European-Finnish (FIN) AF: 0.249 AC: 2627 AN: 10548

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 23975 AN: 67942

Other (OTH) AF: 0.277 AC: 586 AN: 2114

Alfa AF: 0.289 Hom.: 1262

Bravo AF: 0.263

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.18
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: rs1520229; hg19: chr16-65063629;