chr16-64952330-G-A

Position:

• chr16-64952330-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDH11	NM_001797.4	c.1643-1312C>T		intron_variant		ENST00000268603.9
CDH11	NM_001308392.2	c.1643-1312C>T		intron_variant
CDH11	NM_001330576.2	c.1265-1312C>T		intron_variant
CDH11	XM_047433486.1	c.1265-1312C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDH11	ENST00000268603.9	c.1643-1312C>T		intron_variant		1	NM_001797.4	P1
CDH11	ENST00000394156.7	c.1643-1312C>T		intron_variant		1
CDH11	ENST00000566827.5	c.1265-1312C>T		intron_variant		2

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

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.665

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.470

Alfa AF: 0.488 Hom.: 4366

Bravo AF: 0.469

Asia WGS AF: 0.545 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	12
DANN	Benign	0.72

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: rs35143; hg19: chr16-64986233;