chr5-24607337-C-T

Variant names:

• chr5-24607337-C-T
• rs9293140
• NM_006727.5:c.-123-13724G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006727.5(CDH10):​c.-123-13724G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 151,870 control chromosomes in the GnomAD database, including 8,172 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 0.30 (8172 hom., cov: 32)
• Consequence: CDH10 NM_006727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 4 publications found

Genes affected

CDH10 (HGNC:1749): (cadherin 10) This gene encodes a type II classical cadherin of the cadherin superfamily. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate the mature cadherin protein. These integral membrane proteins mediate calcium-dependent cell-cell adhesion and are composed of a large N-terminal extracellular domain, a single membrane-spanning domain, and a small, highly conserved C-terminal cytoplasmic domain. The extracellular domain consists of 5 subdomains, each containing a cadherin motif, and appears to determine the specificity of the protein's homophilic cell adhesion activity. Type II (atypical) cadherins are defined based on their lack of a histidine-alanine-valine (HAV) cell adhesion recognition sequence specific to type I cadherins. This particular cadherin is predominantly expressed in brain and is putatively involved in synaptic adhesions, axon outgrowth and guidance. Mutations in this gene may be associated with lung squamous cell carcinoma and colorectal cancer in human patients. [provided by RefSeq, Nov 2015]

ENSG00000251294 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006727.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH10	NM_006727.5	MANE Select	c.-123-13724G>A		intron	N/A	NP_006718.2
	CDH10	NM_001317224.2		c.-123-13724G>A		intron	N/A	NP_001304153.1	X5DNG6
	CDH10	NM_001362460.1		c.-123-13724G>A		intron	N/A	NP_001349389.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH10	ENST00000264463.8	TSL:1 MANE Select	c.-123-13724G>A		intron	N/A	ENSP00000264463.4	Q9Y6N8
	CDH10	ENST00000510477.5	TSL:1	n.-123-13724G>A		intron	N/A	ENSP00000425653.1	D6RJG0
	CDH10	ENST00000965911.1		c.-123-13724G>A		intron	N/A	ENSP00000635970.1

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46154 AN: 151752 Hom.: 8149 Cov.: 32

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.264

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.304 AC: 46229 AN: 151870 Hom.: 8172 Cov.: 32 AF XY: 0.304 AC XY: 22554 AN XY: 74214

African (AFR) AF: 0.497 AC: 20560 AN: 41366

American (AMR) AF: 0.201 AC: 3057 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 584 AN: 3470

East Asian (EAS) AF: 0.348 AC: 1798 AN: 5162

South Asian (SAS) AF: 0.260 AC: 1252 AN: 4820

European-Finnish (FIN) AF: 0.278 AC: 2928 AN: 10534

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15171 AN: 67956

Other (OTH) AF: 0.268 AC: 565 AN: 2110

Alfa AF: 0.269 Hom.: 889

Bravo AF: 0.307

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.61
PhyloP100		-0.49
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9293140; hg19: chr5-24607446;