16-64952330-G-A

Variant names:

• chr16-64952330-G-A
• rs35143
• NM_001797.4:c.1643-1312C>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.1643-1312C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,902 control chromosomes in the GnomAD database, including 17,687 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 0.47 (17687 hom., cov: 32)
• Consequence: CDH11 NM_001797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 6 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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH11	NM_001797.4	MANE Select	c.1643-1312C>T		intron	N/A	NP_001788.2
	CDH11	NM_001308392.2		c.1643-1312C>T		intron	N/A	NP_001295321.1
	CDH11	NM_001330576.2		c.1265-1312C>T		intron	N/A	NP_001317505.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH11	ENST00000268603.9	TSL:1 MANE Select	c.1643-1312C>T		intron	N/A	ENSP00000268603.4
	CDH11	ENST00000394156.7	TSL:1	c.1643-1312C>T		intron	N/A	ENSP00000377711.3
	CDH11	ENST00000566827.5	TSL:2	c.1265-1312C>T		intron	N/A	ENSP00000457812.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71864 AN: 151784 Hom.: 17675 Cov.: 32

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.473 AC: 71922 AN: 151902 Hom.: 17687 Cov.: 32 AF XY: 0.479 AC XY: 35555 AN XY: 74232

African (AFR) AF: 0.348 AC: 14381 AN: 41368

American (AMR) AF: 0.557 AC: 8515 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1558 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3438 AN: 5172

South Asian (SAS) AF: 0.559 AC: 2696 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5418 AN: 10542

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34276 AN: 67940

Other (OTH) AF: 0.470 AC: 990 AN: 2106

Alfa AF: 0.484 Hom.: 4405

Bravo AF: 0.469

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.72
PhyloP100		0.46
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: rs35143; hg19: chr16-64986233;