Genetic Variant NM_001797.4:c.-298+19288A>G (chr16-65102592-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001797.4(CDH11):c.-298+19288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,230 control chromosomes in the GnomAD database, including 1,612 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 0.14 ( 1612 hom., cov: 33)

Consequence

CDH11
NM_001797.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.56

Publications

3 publications found

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 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)

CDH11 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CDH11	NM_001797.4 link	c.-298+19288A>G	intron_variant	Intron 1 of 12	ENST00000268603.9	NP_001788.2	P55287-1
CDH11	NM_001308392.2 link	c.-298+19288A>G	intron_variant	Intron 1 of 13		NP_001295321.1	P55287-2
CDH11	NM_001330576.2 link	c.-276+19288A>G	intron_variant	Intron 1 of 11		NP_001317505.1	H3BUU9
CDH11	XM_047433486.1 link	c.-276+21082A>G	intron_variant	Intron 1 of 11		XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603.9 link	c.-298+19288A>G		intron_variant	Intron 1 of 12	1	NM_001797.4	ENSP00000268603.4		P55287-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21171

AN:

152112

Hom.:

1606

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.221

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.207

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.185

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.138

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

GnomAD4 genome

AF:

0.139

AC:

21197

AN:

152230

Hom.:

1612

Cov.:

AF XY:

0.143

AC XY:

10667

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.159

AC:

6618

AN:

41534

American (AMR)

AF:

0.192

AC:

2937

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

521

AN:

3470

East Asian (EAS)

AF:

0.207

AC:

1069

AN:

5172

South Asian (SAS)

AF:

0.129

AC:

621

AN:

4822

European-Finnish (FIN)

AF:

0.185

AC:

1958

AN:

10594

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.102

AC:

6940

AN:

68014

Other (OTH)

AF:

0.138

AC:

291

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

925

1850

2775

3700

4625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.119

Hom.:

157

Bravo

AF:

0.144

Asia WGS

AF:

0.160

AC:

555

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.25

(source)

DANN

Benign

0.40

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over