chr5-24517598-C-A

Position:

• chr5-24517598-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_006727.5(CDH10):​c.815-6084G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 151,974 control chromosomes in the GnomAD database, including 50 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 0.020 (50 hom., cov: 33)
• Consequence: CDH10 NM_006727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.677

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0202 (3064/151974) while in subpopulation AFR AF= 0.0303 (1257/41480). AF 95% confidence interval is 0.0289. There are 50 homozygotes in gnomad4. There are 1462 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH10	NM_006727.5	c.815-6084G>T		intron_variant		ENST00000264463.8	NP_006718.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH10	ENST00000264463.8	c.815-6084G>T		intron_variant		1	NM_006727.5	ENSP00000264463.4
CDH10	ENST00000510477.5	n.815-6084G>T		intron_variant		1		ENSP00000425653.1

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3063 AN: 151856 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.0303

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0282

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00190

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0163

Gnomad OTH AF: 0.0355

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

GnomAD4 genome AF: 0.0202 AC: 3064 AN: 151974 Hom.: 50 Cov.: 33 AF XY: 0.0197 AC XY: 1462 AN XY: 74260

Gnomad4 AFR AF: 0.0303

Gnomad4 AMR AF: 0.0281

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00190

Gnomad4 NFE AF: 0.0163

Gnomad4 OTH AF: 0.0347

Alfa AF: 0.0179 Hom.: 8

Bravo AF: 0.0236

Asia WGS AF: 0.00549 AC: 19 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.37
DANN	Benign	0.39

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: rs10520913; hg19: chr5-24517707;