5-24607337-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDH10	NM_006727.5	c.-123-13724G>A		intron_variant	Intron 1 of 11	ENST00000264463.8	NP_006718.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH10	ENST00000264463.8	c.-123-13724G>A		intron_variant	Intron 1 of 11	1	NM_006727.5	ENSP00000264463.4
CDH10	ENST00000510477.5	n.-123-13724G>A		intron_variant	Intron 1 of 10	1		ENSP00000425653.1
ENSG00000251294	ENST00000510391.1	n.171-2423C>T		intron_variant	Intron 1 of 2	3

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

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.348

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.268

Alfa AF: 0.260 Hom.: 785

Bravo AF: 0.307

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	11
DANN	Benign	0.61

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: rs9293140; hg19: chr5-24607446;