rs7187376

Positions:

• chr16-65102592-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH11	NM_001797.4	c.-298+19288A>G		intron_variant		ENST00000268603.9	NP_001788.2
CDH11	NM_001308392.2	c.-298+19288A>G		intron_variant			NP_001295321.1
CDH11	NM_001330576.2	c.-276+19288A>G		intron_variant			NP_001317505.1
CDH11	XM_047433486.1	c.-276+21082A>G		intron_variant			XP_047289442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH11	ENST00000268603.9	c.-298+19288A>G		intron_variant		1	NM_001797.4	ENSP00000268603	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21171 AN: 152112 Hom.: 1606 Cov.: 33

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.: 33 AF XY: 0.143 AC XY: 10667 AN XY: 74422

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.138

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
DANN	Benign	0.40

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: rs7187376; hg19: chr16-65136495;