rs200234049

chr16-64982054-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_001797.4(CDH11):c.1247C>T(p.Pro416Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000379 in 1,611,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Synonymous variant affecting the same amino acid position (i.e. P416P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

CDH11
NM_001797.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.46

Variant links:

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0229325).

BP6

Variant 16-64982054-G-A is Benign according to our data. Variant chr16-64982054-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 254107.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000046 (7/152048) while in subpopulation AMR AF= 0.000458 (7/15276). AF 95% confidence interval is 0.000215. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CDH11	NM_001797.4 linkuse as main transcript	c.1247C>T	p.Pro416Leu	missense_variant	8/13	ENST00000268603.9
CDH11	NM_001308392.2 linkuse as main transcript	c.1247C>T	p.Pro416Leu	missense_variant	8/14
CDH11	NM_001330576.2 linkuse as main transcript	c.869C>T	p.Pro290Leu	missense_variant	7/12
CDH11	XM_047433486.1 linkuse as main transcript	c.869C>T	p.Pro290Leu	missense_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH11	ENST00000268603.9 linkuse as main transcript	c.1247C>T	p.Pro416Leu	missense_variant	8/13	1	NM_001797.4	P1	P55287-1
CDH11	ENST00000394156.7 linkuse as main transcript	c.1247C>T	p.Pro416Leu	missense_variant	8/14	1			P55287-2
	ENST00000624875.1 linkuse as main transcript	n.1174C>T		non_coding_transcript_exon_variant	1/1
CDH11	ENST00000566827.5 linkuse as main transcript	c.869C>T	p.Pro290Leu	missense_variant	7/12	2

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000459

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000133

AC:

AN:

248748

Hom.:

AF XY:

0.0000893

AC XY:

AN XY:

134330

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000843

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000370

AC:

AN:

1459146

Hom.:

Cov.:

AF XY:

0.0000317

AC XY:

AN XY:

725666

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

Gnomad4 AMR exome

AF:

0.000808

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000991

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.0000906

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Oromandibular-limb hypogenesis spectrum

Benign:1

Likely benign, no assertion criteria provided

research

CHU Sainte-Justine Research Center, University of Montreal

Aug 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

-0.014

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.023

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Benign

0.23

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.091

T;T;T

Polyphen

0.95

P;B;.

Vest4

0.44

MVP

0.41

MPC

0.47

ClinPred

0.22

GERP RS

4.8

Varity_R

0.13

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over