rs16960421

Variant names:

• chr16-83417023-G-T
• rs16960421
• NM_001257.5:c.782-69454G>T

Variant summary

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

The NM_001220488.2(CDH13):​c.923-69454G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,160 control chromosomes in the GnomAD database, including 818 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 0.090 (818 hom., cov: 32)
• Consequence: CDH13 NM_001220488.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 2 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001220488.2. 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.782-69454G>T		intron	N/A	NP_001248.1
	CDH13	NM_001220488.2		c.923-69454G>T		intron	N/A	NP_001207417.1
	CDH13	NM_001220489.2		c.665-69454G>T		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.782-69454G>T		intron	N/A	ENSP00000479395.1
	CDH13	ENST00000268613.14	TSL:2	c.923-69454G>T		intron	N/A	ENSP00000268613.10
	CDH13	ENST00000428848.7	TSL:2	c.665-69454G>T		intron	N/A	ENSP00000394557.3

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13722 AN: 152042 Hom.: 819 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0475

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0504

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0793

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

GnomAD4 genome AF: 0.0903 AC: 13738 AN: 152160 Hom.: 818 Cov.: 32 AF XY: 0.0911 AC XY: 6773 AN XY: 74372

African (AFR) AF: 0.169 AC: 7008 AN: 41492

American (AMR) AF: 0.0474 AC: 725 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.0504 AC: 243 AN: 4818

European-Finnish (FIN) AF: 0.119 AC: 1255 AN: 10574

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0605 AC: 4112 AN: 68014

Other (OTH) AF: 0.0784 AC: 166 AN: 2116

Alfa AF: 0.0779 Hom.: 67

Bravo AF: 0.0879

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.1
DANN	Benign	0.81
PhyloP100		0.24
Mutation Taster		=99/1	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: rs16960421; hg19: chr16-83450628;