5-24497407-G-T

Variant names:

• chr5-24497407-G-T
• rs1505874
• NM_006727.5:c.1515+991C>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.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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CDH10	NM_006727.5	c.1515+991C>A		intron_variant	Intron 9 of 11	ENST00000264463.8	NP_006718.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDH10	ENST00000264463.8	c.1515+991C>A		intron_variant	Intron 9 of 11	1	NM_006727.5	ENSP00000264463.4
CDH10	ENST00000510477.5	n.*67+991C>A		intron_variant	Intron 8 of 10	1		ENSP00000425653.1
CDH10	ENST00000502921.5	n.306+991C>A		intron_variant	Intron 2 of 4	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

African (AFR) AF: 0.264 AC: 10911 AN: 41276

American (AMR) AF: 0.439 AC: 6675 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1748 AN: 3462

East Asian (EAS) AF: 0.245 AC: 1246 AN: 5078

South Asian (SAS) AF: 0.337 AC: 1618 AN: 4808

European-Finnish (FIN) AF: 0.501 AC: 5201 AN: 10390

Middle Eastern (MID) AF: 0.441 AC: 128 AN: 290

European-Non Finnish (NFE) AF: 0.540 AC: 36671 AN: 67868

Other (OTH) AF: 0.433 AC: 911 AN: 2102

Alfa AF: 0.486 Hom.: 38857

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
PhyloP100		0.28
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: rs1505874; hg19: chr5-24497516;