16-64987641-C-A

Position:

• chr16-64987641-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001797.4(CDH11):​c.999+516G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,014 control chromosomes in the GnomAD database, including 6,023 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 0.26 (6019 hom., cov: 32)
  • Exomes 𝑓: 0.29 (4 hom.)
• Consequence: CDH11 NM_001797.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH11	NM_001797.4	c.999+516G>T		intron_variant		ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2	c.999+516G>T		intron_variant			NP_001295321.1
CDH11	NM_001330576.2	c.621+516G>T		intron_variant			NP_001317505.1
CDH11	XM_047433486.1	c.621+516G>T		intron_variant			XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603.9	c.999+516G>T		intron_variant		1	NM_001797.4	ENSP00000268603	P1
CDH11	ENST00000394156.7	c.999+516G>T		intron_variant		1		ENSP00000377711
CDH11	ENST00000619158.1	c.*507G>T		3_prime_UTR_variant	1/1			ENSP00000484650
CDH11	ENST00000566827.5	c.621+516G>T		intron_variant		2		ENSP00000457812

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39902 AN: 151804 Hom.: 6015 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.349

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.293 AC: 27 AN: 92 Hom.: 4 Cov.: 0 AF XY: 0.289 AC XY: 11 AN XY: 38

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.263 AC: 39919 AN: 151922 Hom.: 6019 Cov.: 32 AF XY: 0.256 AC XY: 19030 AN XY: 74226

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.281

Alfa AF: 0.292 Hom.: 1237

Bravo AF: 0.258

Asia WGS AF: 0.170 AC: 592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.18

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: rs35200; hg19: chr16-65021544;