chr16-64947596-G-A

Variant names:

• chr16-64947596-G-A
• rs146428080
• NM_001797.4:c.*7C>T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 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 (no stars).

• 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 no assertion criteria provided 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 -9 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
CDH11	NM_001797.4	c.*7C>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2	c.*495C>T		3_prime_UTR_variant	Exon 14 of 14		NP_001295321.1
CDH11	NM_001330576.2	c.*7C>T		3_prime_UTR_variant	Exon 12 of 12		NP_001317505.1
CDH11	XM_047433486.1	c.*7C>T		3_prime_UTR_variant	Exon 12 of 12		XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603	c.*7C>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_001797.4	ENSP00000268603.4
CDH11	ENST00000394156	c.*495C>T		3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000377711.3
CDH11	ENST00000566827	c.*7C>T		3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000457812.1

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: no assertion criteria provided

Submissions by phenotype

CDH11-related disorder Benign:1

Dec 31, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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;