16-64947596-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001797.4(CDH11):c.*7C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,600,396 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (1 hom.)
• Consequence: CDH11 NM_001797.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.136

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 16-64947596-G-A is Benign according to our data. Variant chr16-64947596-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3060946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0014 (213/152202) while in subpopulation AMR AF= 0.00229 (35/15292). AF 95% confidence interval is 0.00169. There are 1 homozygotes in gnomad4. There are 111 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH11	NM_001797.4	c.*7C>T		3_prime_UTR_variant	13/13	ENST00000268603.9
CDH11	NM_001308392.2	c.*495C>T		3_prime_UTR_variant	14/14
CDH11	NM_001330576.2	c.*7C>T		3_prime_UTR_variant	12/12
CDH11	XM_047433486.1	c.*7C>T		3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH11	ENST00000268603.9	c.*7C>T		3_prime_UTR_variant	13/13	1	NM_001797.4	P1
CDH11	ENST00000394156.7	c.*495C>T		3_prime_UTR_variant	14/14	1
CDH11	ENST00000566827.5	c.*7C>T		3_prime_UTR_variant	12/12	2

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152084 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000994 AC: 247 AN: 248386 Hom.: 0 AF XY: 0.00106 AC XY: 142 AN XY: 134348

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.000943

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.000373

Gnomad NFE exome AF: 0.00177

Gnomad OTH exome AF: 0.000333

GnomAD4 exome AF: 0.00149 AC: 2151 AN: 1448194 Hom.: 1 Cov.: 32 AF XY: 0.00146 AC XY: 1048 AN XY: 717940

Gnomad4 AFR exome AF: 0.000334

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000752

Gnomad4 NFE exome AF: 0.00179

Gnomad4 OTH exome AF: 0.00136

GnomAD4 genome AF: 0.00140 AC: 213 AN: 152202 Hom.: 1 Cov.: 32 AF XY: 0.00149 AC XY: 111 AN XY: 74408

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00178

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00104 Hom.: 0

Bravo AF: 0.00151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CDH11-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 31, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	9.1
Dann	Benign	0.85

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: rs146428080; hg19: chr16-64981499; COSMIC: COSV99220023;