chr16-83074041-G-T

Variant names:

• chr16-83074041-G-T
• rs6565113
• NM_001257.5:c.366+41823G>T

Variant summary

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

The NM_001257.5(CDH13):​c.366+41823G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 151,886 control chromosomes in the GnomAD database, including 28,968 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 0.61 (28968 hom., cov: 31)
• Consequence: CDH13 NM_001257.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 20 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	NM_001257.5	MANE Select	c.366+41823G>T		intron	N/A	NP_001248.1	P55290-1
	CDH13	NM_001220488.2		c.507+41823G>T		intron	N/A	NP_001207417.1	P55290-4
	CDH13	NM_001220489.2		c.366+41823G>T		intron	N/A	NP_001207418.1	P55290-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDH13	ENST00000567109.6	TSL:1 MANE Select	c.366+41823G>T		intron	N/A	ENSP00000479395.1	P55290-1
	CDH13	ENST00000431540.7	TSL:1	c.366+41823G>T		intron	N/A	ENSP00000408632.3	P55290-2
	CDH13	ENST00000268613.14	TSL:2	c.507+41823G>T		intron	N/A	ENSP00000268613.10	P55290-4

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92175 AN: 151766 Hom.: 28919 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.531

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.608 AC: 92283 AN: 151886 Hom.: 28968 Cov.: 31 AF XY: 0.607 AC XY: 45054 AN XY: 74176

African (AFR) AF: 0.784 AC: 32498 AN: 41474

American (AMR) AF: 0.571 AC: 8715 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3468

East Asian (EAS) AF: 0.563 AC: 2887 AN: 5132

South Asian (SAS) AF: 0.534 AC: 2568 AN: 4810

European-Finnish (FIN) AF: 0.591 AC: 6215 AN: 10516

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36130 AN: 67922

Other (OTH) AF: 0.557 AC: 1176 AN: 2110

Alfa AF: 0.544 Hom.: 7770

Bravo AF: 0.615

Asia WGS AF: 0.570 AC: 1982 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.60
PhyloP100		-2.2
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: rs6565113; hg19: chr16-83107646;