16-82686231-T-C

Variant names:

• chr16-82686231-T-C
• rs8060937
• NM_001257.5:c.45+59094T>C

Variant summary

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

The NM_001257.5(CDH13):​c.45+59094T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,194 control chromosomes in the GnomAD database, including 1,862 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 0.15 (1862 hom., cov: 33)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• Publications: 6 publications found

Genes affected

CDH13 (HGNC:1753): (cadherin 13) This gene encodes a member of the cadherin superfamily. The encoded protein is localized to the surface of the cell membrane and is anchored by a GPI moiety, rather than by a transmembrane domain. The protein lacks the cytoplasmic domain characteristic of other cadherins, and so is not thought to be a cell-cell adhesion glycoprotein. This protein acts as a negative regulator of axon growth during neural differentiation. It also protects vascular endothelial cells from apoptosis due to oxidative stress, and is associated with resistance to atherosclerosis. The gene is hypermethylated in many types of cancer. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.45+59094T>C		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.186+46766T>C		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.45+59094T>C		intron	N/A	NP_001207418.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.45+59094T>C		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000431540.7	TSL:1	c.45+59094T>C		intron	N/A	ENSP00000408632.3
	CDH13	ENST00000567445.1	TSL:1	c.45+59094T>C		intron	N/A	ENSP00000456297.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22114 AN: 152076 Hom.: 1860 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.145 AC: 22132 AN: 152194 Hom.: 1862 Cov.: 33 AF XY: 0.148 AC XY: 11031 AN XY: 74414

African (AFR) AF: 0.148 AC: 6143 AN: 41518

American (AMR) AF: 0.172 AC: 2624 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.381 AC: 1962 AN: 5150

South Asian (SAS) AF: 0.184 AC: 886 AN: 4816

European-Finnish (FIN) AF: 0.106 AC: 1127 AN: 10602

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8273 AN: 68022

Other (OTH) AF: 0.167 AC: 354 AN: 2114

Alfa AF: 0.133 Hom.: 2765

Bravo AF: 0.152

Asia WGS AF: 0.256 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.5
DANN	Benign	0.76
PhyloP100		-0.14
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: rs8060937; hg19: chr16-82719836;