rs1520229

Positions:

• chr16-65029726-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
CDH11	NM_001797.4	c.-173+24078C>T		intron_variant		ENST00000268603.9
CDH11	NM_001308392.2	c.-173+24078C>T		intron_variant
CDH11	NM_001330576.2	c.-151+24078C>T		intron_variant
CDH11	XM_047433486.1	c.-151+24078C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH11	ENST00000268603.9	c.-173+24078C>T		intron_variant		1	NM_001797.4	P1

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.277

Alfa AF: 0.294 Hom.: 1253

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

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: rs1520229; hg19: chr16-65063629;