5-24497407-G-T

Position:

• chr5-24497407-G-T

Variant summary

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

The NM_006727.5(CDH10):​c.1515+991C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,384 control chromosomes in the GnomAD database, including 15,431 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 0.43 (15431 hom., cov: 30)
• Consequence: CDH10 NM_006727.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDH10	NM_006727.5	c.1515+991C>A		intron_variant		ENST00000264463.8	NP_006718.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDH10	ENST00000264463.8	c.1515+991C>A		intron_variant		1	NM_006727.5	ENSP00000264463	P1
CDH10	ENST00000510477.5	c.*67+991C>A		intron_variant, NMD_transcript_variant		1		ENSP00000425653
CDH10	ENST00000502921.5	n.306+991C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65547 AN: 151268 Hom.: 15431 Cov.: 30

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.433 AC: 65555 AN: 151384 Hom.: 15431 Cov.: 30 AF XY: 0.427 AC XY: 31526 AN XY: 73906

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.505

Gnomad4 EAS AF: 0.245

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.540

Gnomad4 OTH AF: 0.433

Alfa AF: 0.480 Hom.: 9830

Bravo AF: 0.422

Asia WGS AF: 0.297 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.80

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: rs1505874; hg19: chr5-24497516;